Molecular Biology of the Cell

The cause of position effect variegation in Drosophila.......Page 0
http://www.geocities.com/zrnet76/......Page 2
Acknowledgments......Page 10
Preface......Page 19
A Note to the Reader......Page 22
I. Introduction to the Cell......Page 26
1. Cells and Genomes......Page 28
An egg cell.......Page 29
The Universal Features of Cells on Earth......Page 30
The hereditary information in the egg cell determines the nature of the whole multicellular organism.......Page 39
DNA and its building blocks.......Page 41
The duplication of genetic information by DNA replication.......Page 42
From DNA to protein.......Page 43
How genetic information is broadcast for use inside the cell.......Page 44
The conformation of an RNA molecule.......Page 45
How a protein molecule acts as catalyst for a chemical reaction.......Page 46
Life as an autocatalytic process.......Page 47
Transfer RNA.......Page 48
A ribosome at work.......Page 49
(A) A diagram of a small portion of the genome of the bacterium Escherichia coli, containing genes (called lacI, lacZ, lacY, and lacA) coding for four different proteins.......Page 51
Formation of a membrane by amphipathic phospholipid molecules.......Page 52
Membrane transport proteins.......Page 53
Mycoplasma genitalium.......Page 54
The Diversity of Genomes and the Tree of Life......Page 56
The geology of a hot hydrothermal vent in the ocean floor......Page 69
Living organisms at a hot hydrothermal vent.......Page 70
Shapes and sizes of some bacteria.......Page 71
The structure of a bacterium.......Page 72
The phototrophic bacterium Anabaena cylindrica viewed in the light microscope.......Page 73
A lithotrophic bacterium.......Page 74
The three major divisions (domains) of the living world.......Page 75
Genetic information conserved since the beginnings of life.......Page 76
Four modes of genetic innovation and their effects on the DNA sequence of an organism.......Page 77
Families of evolutionarily related genes in the genome of Bacillus subtilis.......Page 78
Paralogous genes and orthologous genes: two types of gene homology based on different evolutionary pathways.......Page 79
A complex family of homologous genes.......Page 80
The viral transfer of DNA from one cell to another......Page 81
Horizontal gene transfers in early evolution.......Page 83
A mutant phenotype reflecting the function of a gene.......Page 84
The genome of E. coli.......Page 85
Some Genomes That Have Been Completely Sequenced......Page 86
The Numbers of Gene Families, Classified by Function, That Are Common to All Three Domains of the Living World......Page 88
Genetic Information in Eucaryotes......Page 90
The major features of eucaryotic cells.......Page 103
Phagocytosis.......Page 104
A single-celled eucaryote that eats other cells.......Page 105
A mitochondrion.......Page 106
The origin of mitochondria.......Page 107
Chloroplasts.......Page 108
The origin of chloroplasts.......Page 109
Genome sizes compared.......Page 110
The puffer fish (Fugu rubripes).......Page 111
Controlling gene readout by environmental signals.......Page 112
Genetic control of the program of multicellular development.......Page 113
An assortment of protists: a small sample of an extremely diverse class of organisms.......Page 114
The yeast Saccharomyces cerevisiae.......Page 116
The reproductive cycles of the yeast S. cerevisiae.......Page 117
Monitoring changes in yeast gene expression using a DNA array.......Page 118
Arabidopsis thaliana, the plant chosen as the primary model for studying plant molecular genetics.......Page 121
Caenorhabditis elegans, the first multicellular organism to have its complete genome sequence determined.......Page 122
Drosophila melanogaster.......Page 123
Giant chromosomes from salivary gland cells of Drosophila.......Page 124
Two species of the frog genus Xenopus.......Page 125
The consequences of gene duplication for mutational analyses of gene function.......Page 126
Times of divergence of different vertebrates.......Page 127
Human and mouse: similar genes and similar development.......Page 129
References......Page 130
2. Cell Chemistry and Biosynthesis......Page 134
Crowded cytoplasm.......Page 135
The Chemical Components of a Cell......Page 136
Highly schematic representations of an atom of carbon and an atom of hydrogen.......Page 155
Moles and molar solutions.......Page 156
The abundances of some chemical elements in the nonliving world (the Earth\'s crust) compared with their abundances in the tissues of an animal.......Page 157
Filled and unfilled electron shells in some common elements.......Page 158
Comparison of covalent and ionic bonds.......Page 159
Sodium chloride: an example of ionic bond formation.......Page 160
Some energies important for cells.......Page 161
The geometry of covalent bonds.......Page 162
Carbon-carbon double bonds and single bonds compared.......Page 163
Polar and nonpolar covalent bonds.......Page 164
The balance of van der Waals forces between two atoms.......Page 165
Three representations of a water molecule.......Page 166
Acids in water.......Page 167
How the dipoles on water molecules orient to reduce the affinity of oppositely charged ions or polar groups for each other.......Page 168
Hydrogen bonds.......Page 169
How two macro-molecules with complementary surfaces can bind tightly to one another through noncovalent interactions.......Page 170
The four main families of small organic molecules in cells.......Page 171
The structure of glucose, a simple sugar.......Page 172
The reaction of two monosaccharides to form a disaccharide.......Page 173
Eleven disaccharides consisting of two D-glucose units.......Page 174
A fatty acid.......Page 175
Phospholipid structure and the orientation of phospholipids in membranes.......Page 176
The amino acid alanine.......Page 177
A small part of a protein molecule.......Page 178
The charge on amino acid side chains depends on the pH.......Page 179
Chemical structure of adenosine triphosphate (ATP).......Page 181
The ATP molecule serves as an energy carrier in cells.......Page 182
A small part of one chain of a deoxyribonucleic acid (DNA) molecule.......Page 183
Macromolecules are abundant in cells.......Page 185
Three families of macromolecules.......Page 186
Most proteins and many RNA molecules fold into only one stable conformation.......Page 187
Small molecules, proteins, and a ribosome drawn approximately to scale.......Page 188
Atomic Characteristics of the Most Abundant Elements in Living Tissues......Page 189
Covalent and Noncovalent Chemical Bonds......Page 190
The Approximate Chemical Composition of a Bacterial Cell......Page 191
Approximate Chemical Compositions of a Typical Bacterium and a Typical Mammalian Cell......Page 192
Chemical Bonds and Groups Commonly Encountered in Biological Molecules......Page 193
Water and Its Influence on the Behavior of Biological Molecules......Page 197
The Principal Types of Weak Noncovalent Bonds that Hold Macromolecules Together......Page 201
An Outline of Some of the Types of Sugars Commonly Found in Cells......Page 205
Fatty Acids and Other Lipids......Page 209
A Survey of the Nucleotides......Page 213
Catalysis and the Use of Energy by Cells......Page 217
Order in biological structures.......Page 235
How a set of enzyme-catalyzed reactions generates a metabolic pathway.......Page 236
Some of the metabolic pathways and their interconnections in a typical cell.......Page 237
Schematic representation of the relationship between catabolic and anabolic pathways in metabolism.......Page 239
An everyday illustration of the spontaneous drive toward disorder.......Page 240
A simple thermodynamic analysis of a living cell.......Page 241
Some interconversions between different forms of energy.......Page 242
Photosynthesis.......Page 244
Photosynthesis and respiration as complementary processes in the living world.......Page 245
The carbon cycle.......Page 246
Oxidation and reduction.......Page 247
The important principle of activation energy.......Page 248
Lowering the activation energy greatly increases the probability of reaction.......Page 249
Floating ball analogies for enzyme catalysis.......Page 250
How enzymes work.......Page 252
A random walk.......Page 253
The structure of the cytoplasm.......Page 254
The distinction between energetically favorable and energetically unfavorable reactions.......Page 255
How reaction coupling is used to drive energetically unfavorable reactions.......Page 256
Chemical equilibrium.......Page 257
Enzymes cannot change the equilibrium point for reactions.......Page 258
How an energetically unfavorable reaction can be driven by a second, following reaction.......Page 259
Energy transfer and the role of activated carriers in metabolism.......Page 260
A mechanical model illustrating the principle of coupled chemical reactions.......Page 261
The hydrolysis of ATP to ADP and inorganic phosphate.......Page 262
An example of a phosphate transfer reaction.......Page 263
An example of an energetically unfavorable biosynthetic reaction driven by ATP hydrolysis.......Page 264
NADPH, an important carrier of electrons.......Page 265
The final stage in one of the biosynthetic routes leading to cholesterol.......Page 267
The structure of the important activated carrier molecule acetyl CoA.......Page 268
A carboxyl group transfer reaction using an activated carrier molecule.......Page 269
Condensation and hydrolysis as opposite reactions.......Page 271
The synthesis of polysaccharides, proteins, and nucleic acids.......Page 272
An alternative route for the hydrolysis of ATP, in which pyrophosphate is first formed and then hydrolyzed.......Page 274
Synthesis of a polynucleotide, RNA or DNA, is a multistep process driven by ATP hydrolysis.......Page 275
The orientation of the active intermediates in biological polymerization reactions.......Page 276
Relationship Between the Standard Free- Energy Change, G , and Equilibrium Constant......Page 277
Some Activated Carrier Molecules Widely Used in Metabolism......Page 278
Free Energy and Biological Reactions......Page 279
How Cells Obtain Energy from Food......Page 283
Schematic representation of the controlled stepwise oxidation of sugar in a cell, compared with ordinary burning.......Page 295
Simplified diagram of the three stages of cellular metabolism that lead from food to waste products in animal cells.......Page 296
An outline of glycolysis.......Page 298
Two pathways for the anaerobic breakdown of pyruvate.......Page 300
Energy storage in steps 6 and 7 of glycolysis.......Page 302
Schematic view of the coupled reactions that form NADH and ATP in steps 6 and 7 of glycolysis.......Page 304
Some phosphate bond energies.......Page 305
The oxidation of pyruvate to acetyl CoA and CO 2 .......Page 306
The oxidation of fatty acids to acetyl CoA.......Page 307
Pathways for the production of acetyl CoA from sugars and fats.......Page 309
Simple overview of the citric acid cycle.......Page 310
The structures of GTP and FADH 2 .......Page 311
The generation of an H gradient across a membrane by electron-transport reactions.......Page 312
The final stages of oxidation of food molecules.......Page 313
The storage of sugars and fats in animal and plant cells.......Page 314
How the ATP needed for most plant cell metabolism is made.......Page 316
Some plant seeds that serve as important foods for humans.......Page 317
The nine essential amino acids.......Page 318
Glycolysis and the citric acid cycle provide the precursors needed to synthesize many important biological molecules.......Page 319
Glycolysis and the citric acid cycle are at the center of metabolism.......Page 320
A representation of all of the known metabolic reactions involving small molecules in a yeast cell.......Page 322
Schematic view of the metabolic cooperation between liver and muscle cells.......Page 323
Details of the 10 Steps of Glycolysis......Page 324
The Complete Citric Acid Cycle......Page 328
References......Page 332
3. Proteins......Page 336
Protein structure......Page 337
The Shape and Structure of Proteins......Page 339
A peptide bond.......Page 356
The structural components of a protein.......Page 358
The 20 amino acids found in proteins.......Page 359
Steric limitations on the bond angles in a polypeptide chain.......Page 360
Three types of noncovalent bonds that help proteins fold.......Page 361
How a protein folds into a compact conformation.......Page 362
Hydrogen bonds in a protein molecule.......Page 363
The refolding of a denatured protein.......Page 364
The regular conformation of the polypeptide backbone observed in the helix and the sheet.......Page 365
Two types of sheet structures.......Page 367
The structure of a coiled-coil.......Page 368
A protein formed from four domains.......Page 370
Ribbon models of three different protein domains.......Page 371
The conformations of two serine proteases compared.......Page 372
A comparison of a class of DNA-binding domains, called homeodomains, in a pair of proteins from two organisms separated by more than a billion years of evolution.......Page 373
Percentage of total genes containing one or more copies of the indicated protein domain, as derived from complete genome sequences.......Page 374
The use of short signature sequences to find homologous protein domains.......Page 375
Domain shuffling.......Page 376
The three-dimensional structures of some protein modules.......Page 377
An extended structure formed from a series of in-line protein modules.......Page 378
Two identical protein subunits binding together to form a symmetric protein dimer.......Page 379
A protein molecule containing multiple copies of a single protein subunit.......Page 380
A protein formed as a symmetric assembly of two different subunits.......Page 381
A collection of protein molecules, shown at the same scale.......Page 382
Protein assemblies.......Page 384
Actin filaments.......Page 385
Some properties of a helix.......Page 386
Collagen and elastin.......Page 387
Disulfide bonds.......Page 388
An example of single protein subunit assembly requiring multiple protein-protein contacts.......Page 389
The capsids of some viruses, all shown at the same scale.......Page 390
The structure of a spherical virus.......Page 391
The structure of tobacco mosaic virus (TMV).......Page 393
Three mechanisms of length determination for large protein assemblies.......Page 394
An electron micrograph of bacteriophage lambda.......Page 395
Proteolytic cleavage in insulin assembly.......Page 396
The 20 Amino Acids Found in Proteins......Page 397
Four different Ways of Depicting a Small Protein Domain: the SH2 Domain (Courtesy of David Lawson.)......Page 401
Protein Function......Page 405
The selective binding of a protein to another molecule.......Page 431
The binding site of a protein.......Page 432
An unusually reactive amino acid at the active site of an enzyme.......Page 433
The evolutionary trace method applied to the SH2 domain.......Page 434
Three ways in which two proteins can bind to each other.......Page 435
An antibody molecule.......Page 436
How noncovalent bonds mediate interactions between macromolecules.......Page 437
Relating binding energies to the equilibrium constant.......Page 438
Enzyme kinetics.......Page 440
Enzymatic acceleration of chemical reactions by decreasing the activation energy.......Page 441
Catalytic antibodies.......Page 442
The rate accelerations caused by five different enzymes.......Page 443
Acid catalysis and base catalysis.......Page 444
The reaction catalyzed by lysozyme.......Page 445
Events at the active site of lysozyme.......Page 446
Some general strategies of enzyme catalysis.......Page 448
Retinal and heme.......Page 449
The structure of pyruvate dehydrogenase.......Page 450
Feedback inhibition of a single biosynthetic pathway.......Page 451
Multiple feedback inhibition.......Page 452
Positive regulation caused by conformational coupling between two distant binding sites.......Page 454
Negative regulation caused by conformational coupling between two distant binding sites.......Page 455
Enzyme activity versus the concentration of inhibitory ligand for single-subunit and multi-subunit allosteric enzymes.......Page 456
A cooperative allosteric transition in an enzyme composed of two identical subunits.......Page 457
The transition between R and T states in the enzyme aspartate transcarbamoylase.......Page 459
Part of the on-off switch in the catalytic subunits of aspartate transcarbamoylase.......Page 461
Protein phosphorylation.......Page 462
The three-dimensional structure of a protein kinase.......Page 463
An evolutionary tree of selected protein kinases.......Page 464
How a Cdk protein acts as an integrating device.......Page 465
The domain structure of the Src family of protein kinases, mapped along the amino acid sequence.......Page 466
The activation of a Src-type protein kinase by two sequential events.......Page 467
How a Src-type protein kinase acts as an integrating device.......Page 469
GTP-binding proteins as molecular switches.......Page 470
The structure of the Ras protein in its GTP-bound form.......Page 471
A comparison of the two major intracellular signaling mechanisms in eucaryotic cells.......Page 472
An aminoacyl tRNA molecule bound to EF-Tu.......Page 473
The large conformational change in EF-Tu caused by GTP hydrolysis.......Page 474
An allosteric walking protein.......Page 475
An allosteric motor protein.......Page 476
The transport of calcium ions by the Ca 2+ pump.......Page 477
A map of the protein-protein interactions observed between different functional groups of proteins in the yeast S. cerevisiae.......Page 478
Some Common Types of Enzymes......Page 479
Many Vitamins Provide Critical Coenzymes for Human Cells......Page 481
Some of the Methods Used to Study Enzymes......Page 482
References......Page 486
II. Basic Genetic Mechanisms......Page 491
4. DNA and Chromosomes......Page 492
Chromosomes in cells.......Page 495
Experimental demonstration that DNA is the genetic material.......Page 496
The nucleosome.......Page 497
The Structure and Function of DNA......Page 499
DNA and its building blocks.......Page 503
Complementary base pairs in the DNA double helix.......Page 505
The DNA double helix.......Page 506
The relationship between genetic information carried in DNA and proteins.......Page 507
The nucleotide sequence of the human -globin gene.......Page 508
DNA as a template for its own duplication.......Page 510
A cross-sectional view of a typical cell nucleus.......Page 511
Chromosomal DNA and Its Packaging in the Chromatin Fiber......Page 512
Human chromosomes.......Page 526
The banding patterns of human chromosomes.......Page 527
An aberrant human chromosome.......Page 529
The genome of S. cerevisiae (budding yeast).......Page 530
Two closely related species of deer with very different chromosome numbers.......Page 531
The organization of genes on a human chromosome.......Page 532
Scale of the human genome.......Page 534
Representation of the nucleotide sequence content of the human genome.......Page 535
Conserved synteny between the human and mouse genomes.......Page 536
A proposed evolutionary history of human chromosome 3 and its relatives in other mammals.......Page 537
A simplified view of the eucaryotic cell cycle.......Page 538
A comparison of extended interphase chromatin with the chromatin in a mitotic chromosome.......Page 539
The three DNA sequences required to produce a eucaryotic chromosome that can be replicated and then segregated at mitosis.......Page 540
Nucleosomes as seen in the electron microscope.......Page 541
Structural organization of the nucleosome.......Page 542
The structure of a nucleosome core particle, as determined by x-ray diffraction analyses of crystals.......Page 544
The overall structural organization of the core histones.......Page 545
The assembly of a histone octamer.......Page 546
The bending of DNA in a nucleosome.......Page 548
Variations on the Zigzag model for the 30-nm chromatin fiber.......Page 549
Irregularities in the 30-nm fiber.......Page 550
A speculative model for how histone H1 could change the path of DNA as it exits from the nucleosome.......Page 551
A speculative model for histone tails in the formation of the 30-nm fiber.......Page 552
Model for the mechanism of some chromatin remodeling complexes.......Page 553
A cyclic mechanism for nucleosome disruption and re-formation.......Page 554
Covalent modification of core histone tails.......Page 555
Vital Statistics of Human Chromosome 22 and the Entire Human Genome......Page 557
The Global Structure of Chromosomes......Page 559
Lampbrush chromosomes.......Page 573
A model for the structure of a lampbrush chromosome.......Page 575
The entire set of polytene chromosomes in one Drosophila salivary cell.......Page 577
A light micrograph of a portion of a polytene chromosome from Drosophila salivary glands.......Page 579
An electron micrograph of a small section of a Drosophila polytene chromosome seen in thin section.......Page 580
Chromosome puffs.......Page 581
RNA synthesis in chromosome puffs.......Page 582
Polytene chromosomes from C. tentans .......Page 584
A model for the structure of an interphase chromosome.......Page 585
Position effects on gene expression in two different eucaryotic organisms.......Page 586
The cause of position effect variegation in Drosophila.......Page 588
Speculative model for the heterochromatin at the ends of yeast chromosomes.......Page 590
Two speculative models for how the tight packaging of DNA in heterochromatin can be inherited during chromosome replication.......Page 591
The specialized nucleosome formed on centromeres.......Page 592
The structure of a human centromere.......Page 593
The plasticity of human centromere formation.......Page 594
A typical mitotic chromosome at metaphase.......Page 595
A scanning electron micrograph of a region near one end of a typical mitotic chromosome.......Page 596
An electron micrograph of a mitotic chromosome.......Page 597
Chromatin packing.......Page 598
The SMC proteins in condensins.......Page 599
Comparison of the Giemsa pattern of the largest human chromosome (chromosome 1) with that of chimpanzee, gorilla, and orangutan.......Page 600
The polarized orientation of chromosomes found in certain interphase nuclei.......Page 601
A polymer analogy for interphase chromosome organization.......Page 602
Selective painting of two interphase chromosomes in a human peripheral lymphocyte.......Page 603
Specific regions of interphase chromosomes in close proximity to the nuclear envelope.......Page 604
References......Page 605
5. DNA Replication, Repair, and Recombination......Page 610
The Maintenance of DNA Sequences......Page 611
Different proteins evolve at very different rates.......Page 615
DNA Replication Mechanisms......Page 616
The DNA double helix acts as a template for its own duplication.......Page 628
The chemistry of DNA synthesis.......Page 629
DNA synthesis catalyzed by DNA polymerase.......Page 631
The semiconservative nature of DNA replication.......Page 632
Two replication forks moving in opposite directions on a circular chromosome.......Page 633
An incorrect model for DNA replication.......Page 634
The structure of a DNA replication fork.......Page 635
Exonucleolytic proofreading by DNA polymerase during DNA replication.......Page 636
Editing by DNA polymerase.......Page 638
An explanation for the 5 -to-3 direction of DNA chain growth.......Page 639
RNA primer synthesis.......Page 641
The synthesis of one of the many DNA fragments on the lagging strand.......Page 642
The reaction catalyzed by DNA ligase.......Page 643
An assay used to test for DNA helicase enzymes.......Page 644
The structure of a DNA helicase.......Page 645
The effect of single-strand DNA-binding proteins (SSB proteins) on the structure of single-stranded DNA.......Page 646
The structure of the single-strand binding protein from humans bound to DNA.......Page 647
The regulated sliding clamp that holds DNA polymerase on the DNA.......Page 648
A cycle of loading and unloading of DNA polymerase and the clamp protein on the lagging strand.......Page 650
The proteins at a bacterial DNA replication fork.......Page 651
A moving replication fork.......Page 652
A model for strand-directed mismatch repair in eucaryotes.......Page 654
The winding problem that arises during DNA replication.......Page 655
The reversible nicking reaction catalyzed by a eucaryotic DNA topoisomerase I enzyme.......Page 656
A model for topoisomerase II action.......Page 658
The DNA-helix-passing reaction catalyzed by DNA topoisomerase II.......Page 659
A mammalian replication fork.......Page 661
The Three Steps That Give Rise to High-Fidelity DNA Synthesis......Page 662
The Initiation and Completion of DNA Replication in Chromosomes......Page 663
A replication bubble formed by replication fork initiation.......Page 674
DNA replication of a bacterial genome.......Page 675
The proteins that initiate DNA replication in bacteria.......Page 677
Methylation of the E. coli replication origin creates a refractory period for DNA initiation.......Page 679
The experiments that demonstrated the pattern in which replication forks are formed and move on eucaryotic chromosomes.......Page 680
The four successive phases of a standard eucaryotic cell cycle.......Page 681
Different regions of a chromosome are replicated at different times in S phase.......Page 682
The strategy used to identify replication origins in yeast cells.......Page 683
The origins of DNA replication on chromosome III of the yeast S. cerevisiae .......Page 684
An origin of replication in yeast.......Page 685
Deletions that inactivate an origin of replication in humans.......Page 686
A demonstration that histones remain associated with DNA after the replication fork passes.......Page 687
The addition of new histones to DNA behind a replication fork.......Page 688
The structure of telomerase.......Page 690
Telomere replication.......Page 691
The t-loops at the end of mammalian chromosomes.......Page 692
A demonstration that yeast cells control the length of their telomeres.......Page 693
DNA Repair......Page 694
A summary of spontaneous alterations likely to require DNA repair.......Page 701
Depurination and deamination.......Page 702
The thymine dimer.......Page 703
How chemical modifications of nucleotides produce mutations.......Page 704
A comparison of two major DNA repair pathways.......Page 705
The recognition of an unusual nucleotide in DNA by base-flipping.......Page 706
The deamination of DNA nucleotides.......Page 707
Two different types of end-joining for repairing double-strand breaks.......Page 709
Inherited Syndromes with Defects in DNA Repair......Page 710
General Recombination......Page 712
General recombination.......Page 722
A heteroduplex joint.......Page 723
General recombination in meiosis.......Page 724
DNA hybridization.......Page 726
The structure of the RecA and Rad51 protein-DNA filaments.......Page 727
DNA synapsis catalyzed by the RecA protein.......Page 728
Two types of DNA branch migration observed in experiments in vitro.......Page 729
A Holliday junction and its isomerization.......Page 730
Electron micrograph of a Holliday junction.......Page 731
Enzyme-catalyzed double branch migration at a Holliday junction.......Page 732
The resolution of a Holliday junction to produce crossed-over chromosomes.......Page 733
Gene conversion in meiosis.......Page 735
Gene conversion by mismatch correction.......Page 736
The different resolutions of a general recombination intermediate in mitotic and meiotic cells.......Page 737
The mechanism that prevents general recombination from destabilizing a genome that contains repeated sequences.......Page 738
Site-Specific Recombination......Page 739
Three of the many types of mobile genetic elements found in bacteria.......Page 748
Cut-and-paste transposition.......Page 749
The structure of the central intermediate formed by a cut-and-paste transposase.......Page 750
Replicative transposition.......Page 751
The life cycle of a retrovirus.......Page 753
Reverse transcriptase.......Page 755
Transpositional site-specific recombination by a retrovirus or a retroviral-like retrotransposon.......Page 756
Transpositional site-specific recombination by a nonretroviral retrotransposon.......Page 757
The proposed pattern of expansion of the abundant Alu and B1 sequences found in the human and mouse genomes, respectively.......Page 759
A comparison of the -globin gene cluster in the human and mouse genomes, showing the location of transposable elements.......Page 760
Two types of DNA rearrangement produced by conservative site-specific recombination.......Page 761
The insertion of a circular bacteriophage lambda DNA chromosome into the bacterial chromosome.......Page 762
The life cycle of bacteriophage lambda.......Page 763
How a conservative site-specific recombination enzyme is used to turn on a specific gene in a group of cells in a transgenic animal.......Page 765
Three Major Classes of Transposable Elements......Page 767
References......Page 769
6. How Cells Read the Genome: From DNA to Protein......Page 775
Schematic depiction of a portion of chromosome 2 from the genome of the fruit fly Drosophila melanogaster......Page 778
The pathway from DNA to protein.......Page 781
From DNA to RNA......Page 782
Genes can be expressed with different efficiencies.......Page 808
The chemical structure of RNA.......Page 809
Uracil forms base pairs with adenine.......Page 810
RNA can fold into specific structures.......Page 811
DNA transcription produces a single-stranded RNA molecule that is complementary to one strand of DNA.......Page 812
DNA is transcribed by the enzyme RNA polymerase.......Page 813
Transcription of two genes as observed under the electron microscope.......Page 814
The transcription cycle of bacterial RNA polymerase.......Page 815
The structure of a bacterial RNA polymerase.......Page 817
Consensus sequence for the major class of E. coli promoters.......Page 818
The importance of RNA polymerase orientation.......Page 820
Directions of transcription along a short portion of a bacterial chromosome.......Page 821
Structural similarity between a bacterial RNA polymerase and a eucaryotic RNA polymerase II.......Page 822
Initiation of transcription of a eucaryotic gene by RNA polymerase II.......Page 823
Consensus sequences found in the vicinity of eucaryotic RNA polymerase II start points.......Page 825
Three-dimensional structure of TBP (TATA-binding protein) bound to DNA.......Page 826
Transcription initiation by RNA polymerase II in a eucaryotic cell.......Page 827
Superhelical tension in DNA causes DNA supercoiling.......Page 828
Summary of the steps leading from gene to protein in eucaryotes and bacteria.......Page 830
A comparison of the structures of procaryotic and eucaryotic mRNA molecules.......Page 831
The RNA factory concept for eucaryotic RNA polymerase II.......Page 832
The reactions that cap the 5 end of each RNA molecule synthesized by RNA polymerase II.......Page 833
Structure of two human genes showing the arrangement of exons and introns.......Page 834
The RNA splicing reaction.......Page 835
Alternative splicing of the -tropomyosin gene from rat.......Page 836
The consensus nucleotide sequences in an RNA molecule that signal the beginning and the end of most introns in humans.......Page 837
The RNA splicing mechanism.......Page 838
Several of the rearrangements that take place in the spliceosome during pre-mRNA splicing.......Page 840
Two types of splicing errors.......Page 843
Variation in intron and exon lengths in the human, worm, and fly genomes.......Page 844
The exon definition hypothesis.......Page 845
Outline of the mechanisms used for three types of RNA splicing.......Page 846
Abnormal processing of the -globin primary RNA transcript in humans with the disease thalassemia.......Page 849
The two known classes of self-splicing intron sequences.......Page 851
Consensus nucleotide sequences that direct cleavage and polyadenylation to form the 3 end of a eucaryotic mRNA.......Page 853
Some of the major steps in generating the 3 end of a eucaryotic mRNA.......Page 854
Transport of a large mRNA molecule through the nuclear pore complex.......Page 856
Schematic illustration of an export-ready mRNA molecule and its transport through the nuclear pore.......Page 857
Transcription from tandemly arranged rRNA genes, as seen in the electron microscope.......Page 858
The chemical modification and nucleolytic processing of a eucaryotic 45S precursor rRNA molecule into three separate ribosomal RNAs.......Page 859
Modifications of the precursor rRNA by guide RNAs.......Page 860
Electron micrograph of a thin section of a nucleolus in a human fibroblast, showing its three distinct zones.......Page 861
Changes in the appearance of the nucleolus in a human cell during the cell cycle.......Page 862
Nucleolar fusion.......Page 864
The function of the nucleolus in ribosome and other ribonucleoprotein synthesis.......Page 865
Visualization of chromatin and nuclear bodies.......Page 867
Schematic view of subnuclear structures.......Page 869
Principal Types of RNAs Produced in Cells......Page 870
The Three RNA Polymerases in Eucaryotic Cells......Page 871
From RNA to Protein......Page 872
The genetic code.......Page 895
The three possible reading frames in protein synthesis.......Page 896
A tRNA molecule.......Page 897
Wobble base-pairing between codons and anticodons.......Page 898
Structure of a tRNA-splicing endonuclease docked to a precursor tRNA.......Page 900
A few of the unusual nucleotides found in tRNA molecules.......Page 901
Amino acid activation.......Page 902
The structure of the aminoacyl-tRNA linkage.......Page 903
The genetic code is translated by means of two adaptors that act one after another.......Page 904
Hydrolytic editing.......Page 905
The recognition of a tRNA molecule by its aminoacyl-tRNA synthetase.......Page 906
The incorporation of an amino acid into a protein.......Page 907
Ribosomes in the cytoplasm of a eucaryotic cell.......Page 908
A comparison of the structures of procaryotic and eucaryotic ribosomes.......Page 909
The RNA-binding sites in the ribosome.......Page 912
Translating an mRNA molecule.......Page 915
Detailed view of the translation cycle.......Page 917
Structure of the rRNAs in the large subunit of a bacterial ribosome, as determined by x-ray crystallography.......Page 920
Location of the protein components of the bacterial large ribosomal subunit.......Page 922
Structure of the L15 protein in the large subunit of the bacterial ribosome.......Page 923
A possible reaction mechanism for the peptidyl transferase activity present in the large ribosomal subunit.......Page 924
The initiation phase of protein synthesis in eucaryotes.......Page 925
Structure of a typical bacterial mRNA molecule.......Page 927
The final phase of protein synthesis.......Page 928
The structure of a human translation release factor (eRF1) and its resemblance to a tRNA molecule.......Page 930
A polyribosome.......Page 931
The rescue of a bacterial ribosome stalled on an incomplete mRNA molecule.......Page 932
Incorporation of selenocysteine into a growing polypeptide chain.......Page 934
The translational frameshifting that produces the reverse transcriptase and integrase of a retrovirus.......Page 935
Steps in the creation of a functional protein.......Page 936
The structure of a molten globule.......Page 937
The co-translational folding of a protein.......Page 938
A current view of protein folding.......Page 939
The hsp70 family of molecular chaperones.......Page 940
The structure and function of the hsp60 family of molecular chaperones.......Page 941
The cellular mechanisms that monitor protein quality after protein synthesis.......Page 944
The proteasome.......Page 945
Ubiquitin and the marking of proteins with multiubiquitin chains.......Page 946
Two general ways of inducing the degradation of a specific protein.......Page 947
Protein aggregates that cause human disease.......Page 949
The production of a protein by a eucaryotic cell.......Page 950
Inhibitors of Protein or RNA Synthesis......Page 952
The RNA World and the Origins of Life......Page 953
Time line for the universe, suggesting the early existence of an RNA world of living systems.......Page 960
An RNA molecule that can catalyze its own synthesis.......Page 961
Structures of RNA and two related information-carrying polymers.......Page 962
Common elements of RNA secondary structure.......Page 963
Examples of RNA tertiary interactions.......Page 965
(above) A ribozyme.......Page 966
(left) In vitro selection of a synthetic ribozyme.......Page 968
An RNA molecule that folds into two different ribozymes.......Page 970
A family of mutually supportive RNA molecules, one catalyzing the reproduction of the others.......Page 971
Formation of membrane by phospholipids.......Page 972
The hypothesis that RNA preceded DNA and proteins in evolution.......Page 973
Some Biochemical Reactions That Can Be Catalyzed by Ribozymes......Page 975
References......Page 976
7. Control of Gene Expression......Page 981
An Overview of Gene Control......Page 982
A mammalian neuron and a lymphocyte.......Page 986
Evidence that a differentiated cell contains all the genetic instructions necessary to direct the formation of a complete organism.......Page 988
Differences in mRNA expression patterns among different types of human cancer cells.......Page 990
Differences in the proteins expressed by two human tissues.......Page 992
Six steps at which eucaryotic gene expression can be controlled.......Page 993
DNA-Binding Motifs in Gene Regulatory Proteins......Page 994
Double-helical structure of DNA.......Page 1005
How the different base pairs in DNA can be recognized from their edges without the need to open the double helix.......Page 1006
A DNA recognition code.......Page 1007
Electron micrograph of fragments of a highly bent segment of DNA double helix.......Page 1008
DNA deformation induced by protein binding.......Page 1009
The bending of DNA induced by the binding of the catabolite activator protein (CAP).......Page 1010
The binding of a gene regulatory protein to the major groove of DNA.......Page 1011
The DNA-binding helix-turn-helix motif.......Page 1012
Some helix-turn-helix DNA-binding proteins.......Page 1013
A specific DNA sequence recognized by the bacteriophage lambda Cro protein.......Page 1014
A homeodomain bound to its specific DNA sequence.......Page 1015
One type of zinc finger protein.......Page 1016
DNA binding by a zinc finger protein.......Page 1017
A dimer of the zinc finger domain of the intracellular receptor family bound to its specific DNA sequence.......Page 1018
The bacterial met repressor protein.......Page 1019
A leucine zipper dimer bound to DNA.......Page 1020
Heterodimerization of leucine zipper proteins can alter their DNA-binding specificity.......Page 1021
A heterodimer composed of two homeodomain proteins bound to its DNA recognition site.......Page 1022
Two DNA-binding domains covalently joined by a flexible polypeptide.......Page 1023
A helix-loop-helix dimer bound to DNA.......Page 1024
Inhibitory regulation by truncated HLH proteins.......Page 1025
One of the most common protein-DNA interactions.......Page 1026
Summary of sequence-specific interactions between different six zinc fingers and their DNA recognition sequences.......Page 1027
A gel-mobility shift assay.......Page 1029
DNA affinity chromatography.......Page 1030
A method for determining the DNA sequence recognized by a gene regulatory protein.......Page 1031
Chromatin immunoprecipitation.......Page 1033
Some Gene Regulatory Proteins and the DNA Sequences That They Recognize......Page 1035
How Genetic Switches Work......Page 1037
The clustered genes in E. coli that code for enzymes that manufacture the amino acid tryptophan.......Page 1054
Switching the tryptophan genes on and off.......Page 1055
The binding of tryptophan to the tryptophan repressor protein changes the conformation of the repressor.......Page 1056
Summary of the mechanisms by which specific gene regulatory proteins control gene transcription in procaryotes.......Page 1057
Some bacterial gene regulatory proteins can act as both a transcriptional activator and a repressor, depending on the precise placement of its binding sites in DNA.......Page 1059
Dual control of the lac operon.......Page 1060
Binding of two proteins to separate sites on the DNA double helix can greatly increase their probability of interacting.......Page 1062
Gene activation at a distance.......Page 1064
The gene control region of a typical eucaryotic gene.......Page 1065
The modular structure of a gene activator protein.......Page 1066
Activation of transcription initiation in eucaryotes by recruitment of the eucaryotic RNA polymerase II holoenzyme complex.......Page 1068
A model for the action of some eucaryotic transcriptional activators.......Page 1070
Local alterations in chromatin structure directed by eucaryotic gene activator proteins.......Page 1071
Two specific ways that local histone acetylation can stimulate transcription initiation.......Page 1072
Transcriptional synergy.......Page 1074
An order of events leading to transcription initiation at a specific promoter.......Page 1075
Five ways in which eucaryotic gene repressor proteins can operate.......Page 1076
Eucaryotic gene regulatory proteins often assemble into complexes on DNA.......Page 1078
Schematic depiction of an enhancesome.......Page 1079
The nonuniform distribution of four gene regulatory proteins in an early Drosophila embryo.......Page 1080
The seven stripes of the protein encoded by the even-skipped (eve) gene in a developing Drosophila embryo.......Page 1081
Experiment demonstrating the modular construction of the eve gene regulatory region.......Page 1082
Close-up view of the eve stripe 2 unit.......Page 1083
Distribution of the gene regulatory proteins responsible for ensuring that eve is expressed in stripe 2.......Page 1084
Integration at a promoter.......Page 1085
Some ways in which the activity of gene regulatory proteins is regulated in eucaryotic cells.......Page 1086
Model for the control of the human -globin gene.......Page 1088
The cluster of -like globin genes in humans.......Page 1089
Schematic diagram summarizing the properties of insulators.......Page 1090
Localization of a Drosophila insulator-binding protein on polytene chromosomes.......Page 1091
Interchangeable RNA polymerase subunits as a strategy to control gene expression in a bacterial virus.......Page 1092
Sigma Factors of E. coli......Page 1093
The Molecular Genetic Mechanisms That Create Specialized Cell Types......Page 1094
Switching gene expression by DNA inversion in bacteria.......Page 1113
Control of cell type in yeasts.......Page 1114
Cassette model of yeast mating-type switching.......Page 1116
A simplified version of the regulatory system that determines the mode of growth of bacteriophage lambda in the E. coli host cell.......Page 1117
Schematic diagram showing how a positive feedback loop can create cell memory.......Page 1118
A simple gene clock designed in the laboratory.......Page 1119
Outline of the mechanism of the circadian clock in Drosophila cells.......Page 1120
A single gene regulatory protein can coordinate the expression of several different genes.......Page 1121
Role of the myogenic regulatory proteins in muscle development.......Page 1123
The importance of combinatorial gene control for development.......Page 1125
Expression of the Drosophila ey gene in precursor cells of the leg triggers the development of an eye on the leg.......Page 1127
Gene regulatory proteins that specify eye development in Drosophila.......Page 1128
A general scheme that permits the direct inheritance of states of gene expression during DNA replication.......Page 1129
X-inactivation.......Page 1130
Mammalian X-chromosome inactivation.......Page 1131
Localization of dosage compensation proteins to the X chromosomes of C. elegans hermaphrodite (XX) nuclei.......Page 1132
Formation of 5-methylcytosine occurs by methylation of a cytosine base in the DNA double helix.......Page 1133
How DNA methylation patterns are faithfully inherited.......Page 1134
How DNA methylation may help turn off genes.......Page 1135
Imprinting in the mouse.......Page 1137
Mechanism of imprinting of the mouse Igf2 gene.......Page 1139
The CG islands surrounding the promoter in three mammalian housekeeping genes.......Page 1140
A mechanism to explain both the marked overall deficiency of CG sequences and their clustering into CG islands in vertebrate genomes.......Page 1141
Posttranscriptional Controls......Page 1142
Possible post-transcriptional controls on gene expression.......Page 1159
Four patterns of alternative RNA splicing.......Page 1160
Alternative splicing of RNA transcripts of the Drosophila DSCAM gene.......Page 1161
Negative and positive control of alternative RNA splicing.......Page 1162
Sex determination in Drosophila.......Page 1163
The cascade of changes in gene expression that determines the sex of a fly through alternative RNA splicing.......Page 1164
Regulation of the site of RNA cleavage and poly-A addition determines whether an antibody molecule is secreted or remains membrane-bound.......Page 1166
RNA editing in the mitochondria of trypanosomes.......Page 1169
Mechanism of A-to-I RNA editing in mammals.......Page 1170
The compact genome of HIV, the human AIDS virus.......Page 1171
Regulation of nuclear export by the HIV Rev protein.......Page 1172
Three mechanisms for the localization of mRNAs.......Page 1173
The importance of the 3 UTR in localizing mRNAs to specific regions of the cytoplasm.......Page 1175
Negative translational control.......Page 1176
The elF-2 cycle.......Page 1177
Two mechanisms of translation initiation.......Page 1178
Two mechanisms of eucaryotic mRNA decay.......Page 1179
The competition between mRNA translation and mRNA decay.......Page 1180
Two posttranslational controls mediated by iron.......Page 1181
A model for nonsense-mediated mRNA decay.......Page 1182
The mechanism of RNA interference.......Page 1183
How Genomes Evolve......Page 1184
A phylogenetic tree showing the relationship between the human and the great apes based on nucleotide sequence data.......Page 1199
Tracing the ancestor sequence from a sequence comparison of the coding regions of human and chimpanzee leptin genes.......Page 1200
Comparison of a portion of the mouse and human leptin genes.......Page 1202
A comparison of the -globin gene cluster in the human and mouse genomes, showing the location of transposable elements.......Page 1203
The puffer fish, Fugu rubripes.......Page 1204
Comparison of the genomic sequences of the human and Fugu genes encoding the protein huntingtin.......Page 1205
A phylogenetic tree based on the inferred protein sequences for all nuclear hormone receptors encoded in the genomes of human (H. sapiens), a nematode worm (C. elegans), and a fruit fly (D. melanogaster).......Page 1206
A comparison of the structure of one-chain and four-chain globins.......Page 1207
An evolutionary scheme for the globin chains that carry oxygen in the blood of animals.......Page 1208
Schematic view of an antibody (immunoglobulin) molecule.......Page 1209
Domain structure of a group of evolutionary related proteins that are thought to have a similar function.......Page 1210
Gene control regions for mouse and chicken eye lens crystallins.......Page 1211
References......Page 1213
III. Methods......Page 1219
8. Manipulating Proteins, DNA, and RNA......Page 1220
Microscopic life.......Page 1222
Plant cells in culture.......Page 1223
Isolating Cells and Growing Them in Culture......Page 1224
A fluorescence-activated cell sorter.......Page 1231
Microdissection techniques allow selected cells to be isolated from tissue slices.......Page 1232
Cells in culture.......Page 1233
The production of hybrid cells.......Page 1235
Preparation of hybridomas that secrete monoclonal antibodies against a particular antigen.......Page 1236
Composition of a Typical Medium Suitable for the Cultivation of Mammalian Cells......Page 1238
Some Commonly Used Cell Lines......Page 1240
Some Landmarks in the Development of Tissue and Cell Culture......Page 1241
Fractionation of Cells......Page 1243
The preparative ultracentrifuge.......Page 1253
Cell fractionation by centrifugation.......Page 1254
Comparison of velocity sedimentation and equilibrium sedimentation.......Page 1256
The separation of molecules by column chromatography.......Page 1258
Three types of matrices used for chromatography.......Page 1259
Protein purification by chromatography.......Page 1261
The detergent sodium dodecyl sulfate (SDS) and the reducing agent -mercaptoethanol.......Page 1263
SDS polyacrylamide-gel electrophoresis (SDS-PAGE).......Page 1264
Analysis of protein samples by SDS polyacrylamide-gel electrophoresis.......Page 1265
Separation of protein molecules by isoelectric focusing.......Page 1266
Two-dimensional polyacrylamide-gel electrophoresis.......Page 1267
Western blotting.......Page 1268
Production of a peptide map, or fingerprint, of a protein.......Page 1269
Mass-spectrometric approaches to identify proteins and sequence peptides.......Page 1271
Some Major Events in the Development of Cell-Free Systems......Page 1272
Landmarks in the Development of Chromatography and Electrophoresis and their Applications to Protein Molecules......Page 1273
Some Reagents Commonly Used to Cleave Peptide Bonds in Proteins......Page 1274
Isolating, Cloning, and Sequencing DNA......Page 1275
The DNA nucleotide sequences recognized by four widely used restriction nucleases.......Page 1292
Restriction nucleases produce DNA fragments that can be easily joined together.......Page 1293
Gel electrophoresis techniques for separating DNA molecules by size.......Page 1294
Methods for labeling DNA molecules in vitro.......Page 1296
Different hybridization conditions allow less than perfect DNA matching.......Page 1298
The use of nucleic acid hybridization to determine the region of a cloned DNA fragment that is present in an mRNA molecule.......Page 1299
Detection of specific RNA or DNA molecules by gel-transfer hybridization.......Page 1300
In situ hybridization to locate specific genes on chromosomes.......Page 1303
In situ hybridization for RNA localization.......Page 1304
The insertion of a DNA fragment into a bacterial plasmid with the enzyme DNA ligase.......Page 1305
Purification and amplification of a specific DNA sequence by DNA cloning in a bacterium.......Page 1306
The making of a yeast artificial chromosome (YAC).......Page 1307
Construction of a human genomic DNA library.......Page 1308
The synthesis of cDNA.......Page 1310
The differences between cDNA clones and genomic DNA clones derived from the same region of DNA.......Page 1312
The enzymatic or dideoxy method of sequencing DNA.......Page 1313
Automated DNA sequencing.......Page 1316
Finding the regions in a DNA sequence that encode a protein.......Page 1317
Amplification of DNA using the PCR technique.......Page 1318
Use of PCR to obtain a genomic or cDNA clone.......Page 1321
How PCR is used in forensic science.......Page 1323
Production of large amounts of a protein from a protein-coding DNA sequence cloned into an expression vector and introduced into cells.......Page 1326
Production of large amounts of a protein by using a plasmid expression vector.......Page 1327
Knowledge of the molecular biology of cells makes it possible to experimentally move from gene to protein and from protein to gene.......Page 1328
Some Major Steps in the Development of Recombinant DNA and Transgenic Technology......Page 1329
Analyzing Protein Structure and Function......Page 1331
X-ray crystallography.......Page 1342
NMR spectroscopy.......Page 1344
Results of a BLAST search.......Page 1345
Epitope tagging allows the localization or purification of proteins.......Page 1346
Fluorescence resonance energy transfer (FRET).......Page 1347
Purification of protein complexes using a GST-tagged fusion protein.......Page 1348
The yeast two-hybrid system for detecting protein-protein interactions.......Page 1349
The phage display method for investigating protein interactions.......Page 1350
Surface plasmon resonance.......Page 1351
The DNA footprinting technique.......Page 1353
Landmarks in the Development of X-ray Crystallography and NMR and Their Application to Biological Molecules......Page 1355
Studying Gene Expression and Function......Page 1357
Insertional mutant of the snapdragon, Antirrhinum.......Page 1376
Screens can detect mutations that affect an animal\'s behavior.......Page 1377
Screening for temperature-sensitive bacterial or yeast mutants.......Page 1378
Using genetics to determine the order of function of genes.......Page 1379
Genetic linkage analysis using physical markers on the DNA to find a human gene.......Page 1380
Domain fusions reveal relationships between functionally linked genes.......Page 1381
Using a reporter protein to determine the pattern of a gene\'s expression.......Page 1382
Using DNA microarrays to monitor the expression of thousands of genes simultaneously.......Page 1383
Using cluster analysis to identify sets of genes that are coordinately regulated.......Page 1385
Gene replacement, gene knockout, and gene addition.......Page 1386
The antisense RNA strategy for generating dominant negative mutations.......Page 1387
Dominant negative mutations created by RNA interference.......Page 1388
A dominant negative effect of a protein.......Page 1389
Ectopic misexpression of Wnt, a signaling protein that affects development of the body axis in the early Xenopus embryo.......Page 1390
The use of a synthetic oligonucleotide to modify the protein-coding region of a gene by site-directed mutagenesis.......Page 1391
Summary of the procedures used for making gene replacements in mice.......Page 1393
Mouse with an engineered defect in fibroblast growth factor 5 (FGF5).......Page 1395
A procedure used to make a transgenic plant.......Page 1396
Making collections of mutant organisms.......Page 1398
Review of Classical Genetics......Page 1399
References......Page 1403
9. Visualizing Cells......Page 1408
Looking at the Structure of Cells in the Microscope......Page 1410
A sense of scale between living cells and atoms.......Page 1427
Resolving power.......Page 1429
A light microscope.......Page 1431
Interference between light waves.......Page 1432
Edge effects.......Page 1433
Numerical aperture.......Page 1434
Two ways to obtain contrast in light microscopy.......Page 1435
Four types of light microscopy.......Page 1436
Image processing.......Page 1437
Making tissue sections.......Page 1439
A stained tissue section......Page 1440
The optical system of a fluorescence microscope.......Page 1441
Fluorescent dyes.......Page 1442
Multiple-fluorescent-probe microscopy.......Page 1443
Immunofluorescence.......Page 1444
Indirect immuno-cytochemistry.......Page 1445
Image deconvolution.......Page 1446
The confocal fluorescence microscope.......Page 1447
Conventional and confocal fluorescence microscopy compared.......Page 1448
Three-dimensional reconstruction from confocal microscope images.......Page 1449
The limit of resolution of the electron microscope.......Page 1452
The principal features of a light microscope and a transmission electron microscope.......Page 1453
Two common chemical fixatives used for electron microscopy.......Page 1454
The copper grid that supports the thin sections of a specimen in a TEM.......Page 1455
A root-tip cell stained with osmium and other heavy metal ions.......Page 1456
Localizing proteins in the electron microscope.......Page 1458
A three-dimensional reconstruction from serial sections.......Page 1459
A developing wheat flower, or spike.......Page 1460
The scanning electron microscope.......Page 1461
Scanning electron microscopy.......Page 1462
The nuclear pore.......Page 1463
The preparation of a metal-shadowed replica of the surface of a specimen.......Page 1464
The thylakoid membranes from the chloroplast of a plant cell.......Page 1465
A regular array of protein filaments in an insect muscle.......Page 1466
Negatively stained actin filaments.......Page 1467
EM tomography.......Page 1468
The three-dimensional structure of the 70S ribosome from E. coli determined by EM tomography.......Page 1469
Some Important Discoveries in the History of Light Microscopy......Page 1470
Major Events in the Development of the Electron Microscope and Its Application to Cell Biology......Page 1472
Visualizing Molecules in Living Cells......Page 1474
Aequorin, a luminescent protein.......Page 1482
Visualizing intracellular Ca 2 concentrations by using a fluorescent indicator.......Page 1484
Methods of introducing a membrane-impermeant substance into a cell.......Page 1485
Caged molecules.......Page 1487
Determining microtubule flux in the mitotic spindle with caged fluorescein linked to tubulin.......Page 1488
Green fluorescent protein (GFP).......Page 1490
GFP tagging.......Page 1491
Dynamics of GFP tagging.......Page 1492
The logic of a typical pulse-chase experiment using radioisotopes.......Page 1493
Electron-microscopic autoradiography.......Page 1494
Radioisotopically labeled molecules.......Page 1495
Some Radioisotopes in Common Use in Biological Research......Page 1496
References......Page 1497
IV. Internal Organization of the Cell......Page 1502
10. Membrane Structure......Page 1503
Three views of a cell membrane.......Page 1505
Membrane protein.......Page 1506
The Lipid Bilayer......Page 1508
The parts of a phospholipid molecule.......Page 1516
How hydrophilic and hydrophobic molecules interact differently with water.......Page 1518
Packing arrangements of lipid molecules in an aqueous environment.......Page 1519
The spontaneous closure of a phospholipid bilayer to form a sealed compartment.......Page 1520
Liposomes.......Page 1521
A cross-sectional view of a black membrane, a synthetic lipid bilayer.......Page 1523
Phospholipid mobility.......Page 1524
The influence of cis -double bonds in hydrocarbon chains.......Page 1525
The structure of cholesterol.......Page 1526
Cholesterol in a lipid bilayer.......Page 1527
Four major phospholipids in mammalian plasma membranes.......Page 1528
A lipid raft.......Page 1529
The asymmetrical distribution of phospholipids and glycolipids in the lipid bilayer of human red blood cells.......Page 1530
Some functions of membrane phospholipids in cell signaling.......Page 1531
Glycolipid molecules.......Page 1532
Approximate Lipid Compositions of Different Cell Membranes......Page 1533
Membrane Proteins......Page 1534
Various ways in which membrane proteins associate with the lipid bilayer.......Page 1549
Membrane protein attachment by a fatty acid chain or a prenyl group.......Page 1551
A segment of a transmembrane polypeptide chain crossing the lipid bilayer as an helix.......Page 1553
Using hydropathy plots to localize potential -helical membrane-spanning segments in a polypeptide chain.......Page 1554
barrels formed from different numbers of strands.......Page 1556
A single-pass transmembrane protein.......Page 1558
A detergent micelle in water, shown in cross section.......Page 1559
Solubilizing membrane proteins with a mild detergent.......Page 1560
The structures of two commonly used detergents.......Page 1561
The use of mild detergents for solubilizing, purifying, and reconstituting functional membrane protein systems.......Page 1562
A scanning electron micrograph of human red blood cells.......Page 1564
The preparation of sealed and unsealed red blood cell ghosts and of right-side-out and inside-out vesicles.......Page 1565
SDS polyacrylamide-gel electrophoresis pattern of the proteins in the human red blood cell membrane.......Page 1566
Spectrin molecules from human red blood cells.......Page 1567
The spectrin-based cytoskeleton on the cytosolic side of the human red blood cell membrane.......Page 1568
Converting a single-chain multipass protein into a two-chain multipass protein.......Page 1571
Freeze-fracture electron microscopy.......Page 1572
Freeze-fracture electron micrograph of human red blood cells.......Page 1573
Probable fates of band 3 and glycophorin molecules in the human red blood cell membrane during freeze-fracture.......Page 1574
Drawing of the archaean Halobacterium salinarum showing the patches of purple membrane that contain bacteriorhodopsin molecules.......Page 1575
The three-dimensional structure of a bacteriorhodopsin molecule.......Page 1576
The three-dimensional structure of the photosynthetic reaction center of the bacterium Rhodopseudomonas viridis.......Page 1577
An experiment demonstrating the mixing of plasma membrane proteins on mouse-human hybrid cells.......Page 1579
Measuring the rate of lateral diffusion of a membrane protein by photobleaching techniques.......Page 1581
How a plasma membrane protein is restricted to a particular membrane domain.......Page 1583
Three domains in the plasma membrane of a guinea pig sperm cell.......Page 1584
Four ways of restricting the lateral mobility of specific plasma membrane proteins.......Page 1585
The cell coat, or glycocalyx.......Page 1586
Simplified diagram of the cell coat (glycocalyx).......Page 1587
References......Page 1588
11. Membrane Transport of Small Molecules and the Electrical Properties of Membranes......Page 1592
A Comparison of Ion Concentrations Inside and Outside a Typical Mammalian Cell......Page 1594
Principles of Membrane Transport......Page 1595
The relative permeability of a synthetic lipid bilayer to different classes of molecules.......Page 1599
Permeability coefficients for the passage of various molecules through synthetic lipid bilayers.......Page 1600
Carrier proteins and channel proteins.......Page 1601
Passive and active transport compared.......Page 1602
Ionophores: a channel-former and a mobile ion carrier.......Page 1603
Carrier Proteins and Active Membrane Transport......Page 1604
A model of how a conformational change in a carrier protein could mediate the passive transport of a solute.......Page 1614
The kinetics of simple diffusion and carrier-mediated diffusion.......Page 1615
Three ways of driving active transport.......Page 1616
Three types of carrier-mediated transport.......Page 1617
One way in which a glucose carrier can be driven by a Na gradient.......Page 1618
A model for the molecular mechanism of action of the bacterial lactose permease.......Page 1619
Transcellular transport.......Page 1621
The Na -K pump.......Page 1623
A model of the pumping cycle of the Na -K pump.......Page 1624
A model of how the sarcoplasmic reticulum Ca 2 pump moves Ca 2 .......Page 1625
Response of a human red blood cell to changes in osmolarity of the extracellular fluid.......Page 1628
A small section of the double membrane of an E. coli bacterium.......Page 1629
The auxiliary transport system associated with transport ATPases in bacteria with double membranes.......Page 1630
A typical ABC transporter.......Page 1631
Intracellular Water Balance: the Problem and Its Solution......Page 1632
Ion Channels and the Electrical Properties of Membranes......Page 1634
A typical ion channel, which fluctuates between closed and open conformations.......Page 1656
The gating of ion channels.......Page 1657
The ionic basis of a membrane potential.......Page 1658
The structure of a bacterial K channel.......Page 1659
K specificity of the selectivity filter in a K channel.......Page 1660
A model for the gating of a bacterial K channel.......Page 1661
A typical vertebrate neuron.......Page 1662
An action potential.......Page 1663
The propagation of an action potential along an axon.......Page 1664
The ball-and-chain model of rapid inactivation for a voltage-gated K channel.......Page 1666
Myelination.......Page 1668
The technique of patch-clamp recording.......Page 1670
Patch-clamp measurements for a single voltage-gated Na channel.......Page 1671
A chemical synapse.......Page 1673
A low-magnification scanning electron micrograph of a neuromuscular junction in a frog.......Page 1674
Three conformations of the acetylcholine receptor.......Page 1675
A model for the structure of the acetylcholine receptor.......Page 1676
The system of ion channels at a neuromuscular junction.......Page 1677
A motor neuron cell body in the spinal cord.......Page 1678
The principle of temporal summation.......Page 1680
The encoding of the combined PSP in the form of the frequency of firing of action potentials by an axon.......Page 1681
The signaling events in long-term potentiation.......Page 1682
Some Ion Channel Families......Page 1683
The Derivation of the Nernst Equation......Page 1684
Some Classical Experiments on the Squid Giant Axon......Page 1686
References......Page 1688
12. Intracellular Compartments and Protein Sorting......Page 1692
The endoplasmic reticulum (ER).......Page 1693
The Compartmentalization of Cells......Page 1694
The major intracellular compartments of an animal cell.......Page 1702
An electron micrograph of part of a liver cell seen in cross section.......Page 1703
Development of plastids.......Page 1704
Hypothetical schemes for the evolutionary origins of some membrane-enclosed organelles.......Page 1705
Topological relationships between compartments of the secretory and endocytic pathways in a eucaryotic cell.......Page 1707
A simplified roadmap of protein traffic.......Page 1708
Vesicle budding and fusion during vesicular transport.......Page 1709
Two ways in which a sorting signal can be built into a protein.......Page 1710
Relative Volumes Occupied by the Major Intracellular Compartments in a Liver Cell (Hepatocyte)......Page 1711
Relative Amounts of Membrane Types in Two Kinds of Eucaryotic Cells......Page 1712
Some Typical Signal Sequences......Page 1713
Approaches to Studying Signal Sequences and Protein Translocation Across Membranes......Page 1714
The Transport of Molecules between the Nucleus and the Cytosol......Page 1716
The nuclear envelope.......Page 1725
The arrangement of nuclear pore complexes in the nuclear envelope.......Page 1726
Possible paths for free diffusion through the nuclear pore complex.......Page 1729
The function of a nuclear localization signal.......Page 1730
Visualizing active import through nuclear pores.......Page 1731
Nuclear import receptors.......Page 1732
The compartmentalization of Ran-GDP and Ran-GTP.......Page 1733
A model for how GTP hydrolysis by Ran provides directionality for nuclear transport.......Page 1734
A model for how the binding of Ran-GTP might cause nuclear import receptors to release their cargo.......Page 1735
The control of fly embryo development by nuclear transport.......Page 1736
The control of nuclear import during T-cell activation.......Page 1737
The nuclear lamina.......Page 1738
The breakdown and re-formation of the nuclear envelope during mitosis.......Page 1739
The Transport of Proteins into Mitochondria and Chloroplasts......Page 1741
The subcompartments of mitochondria and chloroplasts.......Page 1749
A signal sequence for mitochondrial protein import.......Page 1750
Three protein translocators in the mitochondrial membranes.......Page 1751
Proteins transiently spanning the inner and outer mitochondrial membranes during their translocation into the matrix.......Page 1752
Protein import by mitochondria.......Page 1753
The role of energy in protein import into the mitochondrial matrix.......Page 1754
Two plausible models of how mitochondrial hsp70 could drive protein import.......Page 1755
Protein import from the cytosol into the inner mitochondrial membrane or intermembrane space.......Page 1756
Translocation of a precursor protein into the thylakoid space of chloroplasts.......Page 1757
Peroxisomes......Page 1759
An electron micrograph of three peroxisomes in a rat liver cell.......Page 1763
The structure of a plasmalogen.......Page 1764
Electron micrographs of two types of peroxisomes found in plant cells.......Page 1765
A model for how new peroxisomes are produced.......Page 1766
The Endoplasmic Reticulum......Page 1767
Fluorescent micrographs of the endoplasmic reticulum.......Page 1785
The rough ER.......Page 1786
Free and membrane-bound ribosomes.......Page 1787
The smooth ER.......Page 1788
The isolation of purified rough and smooth microsomes from the ER.......Page 1789
The signal hypothesis.......Page 1790
The signal-recognition particle (SRP).......Page 1791
How ER signal sequences and SRP direct ribosomes to the ER membrane.......Page 1792
A ribosome bound to the Sec61 protein translocator.......Page 1793
Evidence for a continuous aqueous pore joining the ER lumen and the interior of the ribosome.......Page 1794
Three ways in which protein translocation can be driven through structurally similar translocators.......Page 1795
A model for how a soluble protein is translocated across the ER membrane.......Page 1796
How a single-pass transmembrane protein with a cleaved ER signal sequence is integrated into the ER membrane.......Page 1797
Integration of a single-pass membrane protein with an internal signal sequence into the ER membrane.......Page 1798
Integration of a double-pass membrane protein with an internal signal sequence into the ER membrane.......Page 1800
The insertion of the multipass membrane protein rhodopsin into the ER membrane.......Page 1801
The asparagine-linked (N -linked) precursor oligosaccharide that is added to most proteins in the rough ER membrane.......Page 1802
Protein glycosylation in the rough ER.......Page 1804
Synthesis of the lipid-linked precursor oligosaccharide in the rough ER membrane.......Page 1805
The role of N -linked glycosylation in ER protein folding.......Page 1807
The export and degradation of misfolded ER proteins.......Page 1808
The unfolded protein response in yeast.......Page 1809
The attachment of a GPI anchor to a protein in the ER.......Page 1810
The synthesis of phosphatidylcholine.......Page 1811
The role of phospholipid translocators in lipid bilayer synthesis.......Page 1813
Phospholipid exchange proteins.......Page 1814
References......Page 1815
13. Intracellular Vesicular Traffic......Page 1820
The endocytic and biosynthetic-secretory pathways.......Page 1822
Vesicular transport.......Page 1823
The intracellular compartments of the eucaryotic cell involved in the biosynthetic- secretory and endocytic pathways.......Page 1824
The Molecular Mechanisms of Membrane Transport and the Maintenance of Compartmental Diversity......Page 1825
Electron micrograph of clathrin-coated, COPI-coated, and COPII-coated vesicles.......Page 1835
Utilization of different coats in vesicular traffic.......Page 1836
Clathrin-coated pits and vesicles.......Page 1837
The structure of a clathrin coat.......Page 1838
The assembly and disassembly of a clathrin coat.......Page 1840
The role of dynamin in pinching off clathrin-coated vesicles from the membrane.......Page 1842
A current model of COPII-coated vesicle formation.......Page 1843
The postulated role of SNAREs in guiding vesicular transport.......Page 1844
The structure of paired SNAREs.......Page 1845
Dissociation of SNARE pairs by NSF after a membrane fusion cycle is completed.......Page 1846
A postulated role of Rab proteins in facilitating the docking of transport vesicles.......Page 1847
A model for how SNARE proteins may concentrate in membrane fusion.......Page 1849
The entry of enveloped viruses into cells.......Page 1851
Subcellular Locations of Some Rab Proteins......Page 1854
Strategies Used to Study the Molecular Mechanisms Involved in Vesicular Transport......Page 1855
Transport from the ER through the Golgi Apparatus......Page 1859
The recruitment of cargo molecules into ER transport vesicles.......Page 1872
Retention of incompletely assembled antibody molecules in the ER.......Page 1873
Homotypic membrane fusion.......Page 1874
Vesicular tubular clusters.......Page 1875
A model for the retrieval of ER resident proteins.......Page 1876
The Golgi apparatus.......Page 1878
Light micrographs of the Golgi apparatus.......Page 1880
A goblet cell of the small intestine.......Page 1881
Oligosaccharide processing in the ER and the Golgi apparatus.......Page 1883
The three-dimensional structure of a small N -linked oligosaccharide.......Page 1885
Histochemical stains demonstrating the biochemical compartmentalization of the Golgi apparatus.......Page 1886
The functional compartmentalization of the Golgi apparatus.......Page 1888
Two possible models explaining the organization of the Golgi apparatus and the transport of proteins from one cisterna to the next.......Page 1889
Transport from the Trans Golgi Network to Lysosomes......Page 1890
Lysosomes.......Page 1897
Histochemical visualization of lysosomes.......Page 1898
The plant cell vacuole.......Page 1900
The role of the vacuole in controlling the size of plant cells.......Page 1901
Three pathways to degradation in lysosomes.......Page 1902
The structure of mannose 6-phosphate on a lysosomal enzyme.......Page 1904
The transport of newly synthesized lysosomal hydrolases to lysosomes.......Page 1905
The recognition of a lysosomal hydrolase.......Page 1907
Transport into the Cell from the Plasma Membrane: Endocytosis......Page 1908
Phagocytosis by a macrophage.......Page 1919
Phagocytosis by a neutrophil.......Page 1920
The formation of clathrin-coated vesicles from the plasma membrane.......Page 1921
Caveolae in the plasma membrane of a fibroblast.......Page 1922
A low-density lipoprotein (LDL) particle.......Page 1923
Normal and mutant LDL receptors.......Page 1924
Possible fates for transmembrane receptor proteins that have been endocytosed.......Page 1925
The receptor-mediated endocytosis of LDL.......Page 1926
Sorting of membrane proteins in the endocytic pathway.......Page 1927
Electron micrograph of a multivesicular body in a plant cell.......Page 1929
The endocytic pathway from the plasma membrane to lysosomes.......Page 1930
The sequestration of endocytosed proteins into internal membranes of multivesicular bodies.......Page 1931
Transcytosis.......Page 1932
Storage of plasma membrane proteins in recycling endosomes.......Page 1933
The two distinct early endosomal compartments in an epithelial cell.......Page 1934
Transport from the Trans Golgi Network to the Cell Exterior: Exocytosis......Page 1935
The constitutive and regulated secretory pathways.......Page 1944
The three best-understood pathways of protein sorting in the trans Golgi network.......Page 1945
The formation of secretory vesicles.......Page 1946
Exocytosis of secretory vesicles.......Page 1947
Alternative processing pathways for the prohormone proopiomelanocortin.......Page 1948
Electron micrographs of exocytosis in rat mast cells.......Page 1949
Exocytosis as a localized response.......Page 1950
A comparison of two types of polarized cells.......Page 1951
Two ways of sorting plasma membrane proteins in a polarized epithelial cell.......Page 1952
Model of lipid rafts in the trans Golgi network.......Page 1953
The formation of synaptic vesicles.......Page 1954
References......Page 1955
14. Energy Conversion: Mitochondria and Chloroplasts......Page 1960
Harnessing energy for life.......Page 1963
Chemiosmotic coupling.......Page 1964
Electron transport processes.......Page 1965
The Mitochondrion......Page 1966
Mitochondrial plasticity.......Page 1977
The relationship between mitochondria and microtubules.......Page 1978
Localization of mitochondria near sites of high ATP utilization in cardiac muscle and a sperm tail.......Page 1979
Biochemical fractionation of purified mitochondria into separate components.......Page 1980
The general organization of a mitochondrion.......Page 1982
How electrons are donated by NADH.......Page 1984
A summary of energy-generating metabolism in mitochondria.......Page 1985
The major net energy conversion catalyzed by the mitochondrion.......Page 1987
A comparison of biological oxidations with combustion.......Page 1988
The two components of the electrochemical proton gradient.......Page 1989
The general mechanism of oxidative phosphorylation.......Page 1990
ATP synthase.......Page 1991
Some of the active transport processes driven by the electrochemical proton gradient across the inner mitochondrial membrane.......Page 1992
The rotation of the bacterial flagellum driven by H flow.......Page 1993
The basic relationship between free-energy changes and equilibrium in the ATP hydrolysis reaction.......Page 1994
The ATP synthase is a reversible coupling device that can convert the energy of the electrochemical proton gradient into chemical-bond energy, or vice versa.......Page 1996
Product Yields from the Oxidation of Sugars and Fats......Page 1997
Electron-Transport Chains and Their Proton Pumps......Page 1998
How protons behave in water.......Page 2009
How protons can be pumped across membranes.......Page 2011
The structure of the heme group attached covalently to cytochrome c .......Page 2012
The structures of two types of iron-sulfur centers.......Page 2013
Quinone electron carriers.......Page 2014
The general methods used to determine the path of electrons along an electron-transport chain.......Page 2015
The path of electrons through the three respiratory enzyme complexes.......Page 2016
The reaction of O 2 with electrons in cytochrome oxidase.......Page 2017
The molecular structure of cytochrome oxidase.......Page 2018
Redox potential changes along the mitochondrial electron-transport chain.......Page 2019
The atomic structure of cytochrome b-c 1 .......Page 2021
A general model for H pumping.......Page 2022
The importance of H -driven transport in bacteria.......Page 2023
Redox Potentials......Page 2025
Chloroplasts and Photosynthesis......Page 2027
Plastid diversity.......Page 2040
Electron micrographs of chloroplasts.......Page 2041
The chloroplast.......Page 2044
A mitochondrion and chloroplast compared.......Page 2045
The reactions of photosynthesis in a chloroplast.......Page 2046
The initial reaction in carbon fixation.......Page 2047
The carbon-fixation cycle, which forms organic molecules from CO 2 and H 2 O.......Page 2048
Comparative leaf anatomy in a C 3 plant and a C 4 plant.......Page 2049
The structure of chlorophyll.......Page 2050
Three ways for an excited chlorophyll molecule to return to its original, unexcited state.......Page 2052
The antenna complex and photochemical reaction center in a photosystem.......Page 2053
The arrangement of the electron carriers in a bacterial photochemical reaction center, as determined by x-ray crystallography.......Page 2054
The electron transfers that occur in the photochemical reaction center of a purple bacterium.......Page 2055
Electron flow during photosynthesis in the thylakoid membrane.......Page 2057
Changes in redox potential during photosynthesis.......Page 2058
Three types of photosynthetic reaction centers compared.......Page 2060
A comparison of the flow of H and the orientation of the ATP synthase in mitochondria and chloroplasts.......Page 2062
The Genetic Systems of Mitochondria and Plastids......Page 2064
Mitochondrial and nuclear DNA stained with a fluorescent dye.......Page 2078
The production of mitochondrial and chloroplast proteins by two separate genetic systems.......Page 2079
An electron micrograph of an animal mitochondrial DNA molecule caught during the process of DNA replication.......Page 2080
Dynamic mitochondrial reticulum.......Page 2081
Mitochondrial fission and fusion.......Page 2082
Various sizes of mitochondrial genomes.......Page 2083
A suggested evolutionary pathway for the origin of mitochondria.......Page 2084
Comparison of mitochondrial genomes.......Page 2085
The organization of the human mitochondrial genome.......Page 2086
The organization of the liverwort chloroplast genome.......Page 2087
The difference in the patterns of inheritance between mitochondrial and nuclear genes of yeast cells.......Page 2088
A variegated leaf.......Page 2090
Electron micrographs of yeast cells.......Page 2091
The structure of cardiolipin.......Page 2092
The origins of mitochondrial RNAs and proteins.......Page 2093
Relative Amounts of Organelle DNA in Some Cells and Tissues......Page 2095
Some Differences Between the Universal Code and Mitochondrial Genetic Codes*......Page 2096
The Evolution of Electron-Transport Chains......Page 2097
The oxidation of formic acid in some present-day bacteria.......Page 2103
The evolution of oxidative phosphorylation mechanisms.......Page 2104
Some of the electron-transport pathways in present-day bacteria.......Page 2105
The general flow of electrons in a relatively primitive form of photosynthesis observed in present-day green sulfur bacteria.......Page 2106
Some major events that are believed to have occurred during the evolution of living organisms on Earth.......Page 2107
A phylogenetic tree of the proposed evolution of mitochondria and chloroplasts and their bacterial ancestors.......Page 2108
A comparison of three electron-transport chains discussed in this chapter.......Page 2111
References......Page 2113
15. Cell Communication......Page 2120
A simple intracellular signaling pathway activated by an extracellular signal molecule.......Page 2121
A trimeric GTP-binding protein, or G protein.......Page 2122
General Principles of Cell Communication......Page 2123
Budding yeast cells responding to mating factor.......Page 2142
The binding of extracellular signal molecules to either cell-surface receptors or intracellular receptors.......Page 2143
Forms of intercellular signaling.......Page 2144
The contrast between endocrine and synaptic signaling.......Page 2145
Autocrine signaling.......Page 2147
Signaling via gap junctions.......Page 2148
An animal cell\'s dependence on multiple extracellular signals.......Page 2149
Various responses induced by the neurotransmitter acetylcholine.......Page 2150
The importance of rapid turnover.......Page 2152
The role of nitric oxide (NO) in smooth muscle relaxation in a blood vessel wall.......Page 2153
Some signaling molecules that bind to nuclear receptors.......Page 2154
The nuclear receptor superfamily.......Page 2155
Responses induced by the activation of a nuclear hormone receptor.......Page 2157
Three classes of cell-surface receptors.......Page 2159
Different kinds of intracellular signaling proteins along a signaling pathway from a cell-surface receptor to the nucleus.......Page 2160
Two types of intracellular signaling proteins that act as molecular switches.......Page 2162
Signal integration.......Page 2163
Two types of intracellular signaling complexes.......Page 2164
A hypothetical signaling pathway using modular binding domains.......Page 2166
The primary response of chick oviduct cells to the steroid sex hormone estradiol.......Page 2167
Activation curves as a function of signal-molecule concentration.......Page 2168
One type of signaling mechanism expected to show a steep thresholdlike response.......Page 2169
An accelerating positive feedback mechanism.......Page 2170
Five ways in which target cells can become desensitized to a signal molecule.......Page 2171
Signaling through G-Protein-Linked Cell-Surface Receptors......Page 2172
A G-protein-linked receptor.......Page 2189
The structure of an inactive G protein.......Page 2190
The disassembly of an activated G-protein into two signaling components.......Page 2191
The switching off of the G-protein subunit by the hydrolysis of its bound GTP.......Page 2193
An increase in cyclic AMP in response to an extracellular signal.......Page 2195
The synthesis and degradation of cyclic AMP.......Page 2196
The activation of cyclic-AMP-dependent protein kinase (PKA).......Page 2197
How gene transcription is activated by a rise in cyclic AMP concentration.......Page 2198
Three types of inositol phospholipids (phosphoinositides).......Page 2200
The hydrolysis of PI(4,5)P 2 by phospholipase C- .......Page 2201
The two branches of the inositol phospholipid pathway.......Page 2203
Fertilization of an egg by a sperm triggering an increase in cytosolic Ca 2 .......Page 2204
The main ways eucaryotic cells maintain a very low concentration of free Ca 2 in their cytosol.......Page 2205
Vasopressin-induced Ca 2 oscillations in a liver cell.......Page 2207
The structure of Ca 2 /calmodulin based on x-ray diffraction and NMR studies.......Page 2208
The activation of CaM-kinase II.......Page 2209
CaM-kinase II as a frequency decoder of Ca 2 oscillations.......Page 2211
Olfactory receptor neurons.......Page 2212
Cyclic GMP.......Page 2213
A rod photoreceptor cell.......Page 2214
The response of a rod photoreceptor cell to light.......Page 2216
Amplification in the light-induced catalytic cascade in vertebrate rods.......Page 2217
The roles of G-protein-linked receptor kinases (GRKs) and arrestins in receptor desensitization.......Page 2218
Some Hormone-induced Cell Responses Mediated by Cyclic AMP......Page 2219
Some Cell Responses in Which G-Protein-linked Receptors Activate the Inositol-Phospholipid Signaling Pathway......Page 2220
Three Major Families of Trimeric G Proteins*......Page 2221
Signaling through Enzyme-Linked Cell-Surface Receptors......Page 2222
Seven subfamilies of receptor tyrosine kinases.......Page 2243
Three ways in which signaling proteins can cross-link receptor chains.......Page 2244
Inhibition of signaling through normal receptor tyrosine kinases by an excess of mutant receptors.......Page 2246
The docking of intracellular signaling proteins on an activated receptor tyrosine kinase.......Page 2247
The binding of SH2-containing intracellular signaling proteins to an activated PDGF receptor.......Page 2248
The regulation of Ras activity.......Page 2250
The activation of Ras by an activated receptor tyrosine kinase.......Page 2251
The MAP-kinase serine/threonine phosphorylation pathway activated by Ras.......Page 2252
The organization of MAP-kinase pathways by scaffold proteins in budding yeast.......Page 2253
The generation of inositol phospholipid docking sites by PI 3-kinase.......Page 2254
The recruitment of signaling proteins with PH domains to the plasma membrane during B cell activation.......Page 2255
One way in which signaling through PI 3-kinase promotes cell survival.......Page 2257
Five parallel intracellular signaling pathways activated by G-protein-linked receptors, receptor tyrosine kinases, or both.......Page 2258
The three-dimensional structure of human growth hormone bound to its receptor.......Page 2259
The Jak-STAT signaling pathway activated by -interferon.......Page 2260
Some protein tyrosine phosphatases.......Page 2261
A model for the Smad-dependent signaling pathway activated by TGF- .......Page 2262
Some of the protein kinases discussed in this chapter.......Page 2263
The bacterial flagellar motor.......Page 2266
Positions of the flagella on E. coli during swimming.......Page 2267
The two-component signaling pathway that enables chemotaxis receptors to control the flagellar motor during bacterial chemotaxis.......Page 2268
Some Signaling Proteins That Act Via Receptor Tyrosine Kinases......Page 2270
Some Signaling Proteins That Act Through Cytokine Receptors and the Jak-STAT Signaling Pathway......Page 2271
Signaling Pathways That Depend on Regulated Proteolysis......Page 2272
Lateral inhibition mediated by Notch and Delta during nerve cell development in Drosophila.......Page 2280
The processing and activation of Notch by proteolytic cleavage.......Page 2281
A model for the Wnt activation of the -catenin signaling pathway.......Page 2282
A model for Hedgehog signaling in Drosophila.......Page 2284
The activation of NF- B by TNF- .......Page 2286
Signaling in Plants......Page 2288
The proposed divergence of plant and animal lineages from a common unicellular eucaryotic ancestor.......Page 2294
The three-dimensional structure of leucine-rich repeats, similar to those found in the LRR serine/threonine receptor kinases.......Page 2295
A hypothetical model for CLV1 receptor serine/threonine kinase regulation of cell proliferation and/or differentiation in the shoot meristem.......Page 2296
A current view of the ethylene two-component signaling pathway.......Page 2297
A current view of one way in which phytochromes mediate a light response in plant cells.......Page 2298
References......Page 2299
16. The Cytoskeleton......Page 2303
The cytoskeleton.......Page 2304
The Self-Assembly and Dynamic Structure of Cytoskeletal Filaments......Page 2305
The cytoskeleton and changes in cell shape.......Page 2322
The thermal stability of cytoskeletal filaments with dynamic ends.......Page 2323
A strong filament formed from elongated fibrous subunits with strong lateral contacts.......Page 2324
The time course of actin polymerization in a test tube.......Page 2325
The structure of a microtubule and its subunit.......Page 2326
The structures of an actin monomer and actin filament.......Page 2328
The preferential growth of microtubules at the plus end.......Page 2329
The treadmilling of an actin filament or microtubule, made possible by the nucleoside triphosphate hydrolysis that follows subunit addition.......Page 2330
Treadmilling behavior of a microtubule, as observed in a living cell.......Page 2331
Dynamic instability due to the structural differences between a growing and a shrinking microtubule end.......Page 2333
Direct observation of the dynamic instability of microtubules in a living cell.......Page 2335
The rapid changes in cytoskeletal organization observed during the development of a Drosophila early embryo.......Page 2336
The bacterial FtsZ protein, a tubulin homolog in procaryotes.......Page 2337
Actin at the crossroads.......Page 2339
A model of intermediate filament construction.......Page 2340
Mechanical properties of actin, tubulin, and intermediate filament polymers.......Page 2342
Keratin filaments in epithelial cells.......Page 2343
Blistering of the skin caused by a mutant keratin gene.......Page 2344
Two types of intermediate filaments in cells of the nervous system.......Page 2345
Effect of the drug taxol on microtubule organization.......Page 2346
Major Types of Intermediate Filament Proteins in Vertebrate Cells......Page 2348
Drugs That Affect Actin Filaments and Microtubules......Page 2349
The Three Major Types of Protein that Form the Cytoskeleton......Page 2350
The Polymerization of Actin and Tubulin......Page 2352
How Cells Regulate Their Cytoskeletal Filaments......Page 2356
Polymerization of tubulin nucleated by -tubulin ring complexes.......Page 2373
The centrosome.......Page 2375
A centriole in the centrosome.......Page 2376
The center-seeking behavior of a centrosome.......Page 2377
A microtubule array can find the center of a cell.......Page 2378
The tip of the leading edge of a cell nucleates actin filaments.......Page 2379
Nucleation and actin web formation by the ARP complex.......Page 2380
Profilin bound to an actin monomer.......Page 2381
Effects of thymosin and profilin on actin polymerization.......Page 2382
Effects of stathmin on microtubule polymerization.......Page 2383
Localization of MAPs in axon and dendrites of a neuron.......Page 2384
Organization of microtubule bundles by MAPs.......Page 2385
Twisting of an actin filament induced by cofilin.......Page 2386
Filament capping and its effects on filament dynamics.......Page 2387
The effects of proteins that bind to microtubule ends.......Page 2388
Plectin cross-linking of diverse cytoskeletal elements.......Page 2390
Actin arrays in a cell.......Page 2391
The modular structures of four actin-cross-linking proteins.......Page 2392
The formation of two types of actin filament bundles.......Page 2393
A microvillus.......Page 2394
Filamin cross-links actin filaments into a three-dimensional network with the physical properties of a gel.......Page 2395
Loss of filamin causes abnormal cell motility.......Page 2396
Filament severing and its effects on filament dynamics.......Page 2397
Microtubule severing by katanin.......Page 2398
A model for actin filament severing by gelsolin.......Page 2399
Platelet activation.......Page 2400
The role of ERM-family proteins in attaching actin filaments to the plasma membrane.......Page 2402
Focal contacts and stress fibers in a cultured fibroblast.......Page 2403
The dramatic effects of Rac, Rho, and Cdc42 on actin organization in fibroblasts.......Page 2404
Molecular Motors......Page 2406
Myosin II.......Page 2422
The myosin II bipolar thick filament.......Page 2423
Direct evidence for the motor activity of the myosin head.......Page 2424
Myosin superfamily tree.......Page 2425
Kinesin and kinesin-related proteins.......Page 2427
Dyneins.......Page 2428
X-ray crystal structures of myosin and kinesin heads.......Page 2429
The cycle of structural changes used by myosin to walk along an actin filament.......Page 2430
Comparison of the mechanochemical cycles of kinesin and myosin II.......Page 2431
Orientation of forward- and backward-walking kinesin superfamily proteins bound to microtubules.......Page 2433
The effect of lever arm length on the step size for a motor protein.......Page 2434
Effect of depolymerizing microtubules on the Golgi apparatus.......Page 2435
A model for the attachment of dynein to a membrane-enclosed organelle.......Page 2436
Myosin V on melanosomes.......Page 2437
Regulated melanosome movements in fish pigment cells.......Page 2438
Bidirectional movement of a melanosome on a microtubule.......Page 2440
Light-chain phosphorylation and the regulation of the assembly of myosin II into thick filaments.......Page 2441
Skeletal muscle cells (also called muscle fibers).......Page 2442
Skeletal muscle myofibrils.......Page 2443
Electron micrographs of an insect flight muscle viewed in cross section.......Page 2445
The sliding-filament model of muscle contraction.......Page 2446
Organization of accessory proteins in a sarcomere.......Page 2447
T tubules and the sarcoplasmic reticulum.......Page 2448
The control of skeletal muscle contraction by troponin.......Page 2450
Effect on the heart of a subtle mutation in cardiac myosin.......Page 2451
The contrasting motions of flagella and cilia.......Page 2452
The arrangement of microtubules in a flagellum or cilium.......Page 2454
Ciliary dynein.......Page 2455
The bending of an axoneme.......Page 2456
Basal bodies.......Page 2457
The Cytoskeleton and Cell Behavior......Page 2458
Polarity of actin patches and cables throughout the yeast cell cycle.......Page 2469
Morphological polarization of yeast cells in response to mating factor.......Page 2470
The signaling pathway in the yeast mating factor response.......Page 2471
Polarized mRNA localization in the yeast bud tip.......Page 2472
A model of how forces generated in the actin-rich cortex move a cell forward.......Page 2473
Migratory keratocytes from a fish epidermis.......Page 2474
Behavior of lamellipodial fragments.......Page 2475
Actin filament nucleation and web formation by the ARP complex in lamellipodia.......Page 2476
Cofilin in lamellipodia.......Page 2478
A model for protrusion of the actin meshwork at the leading edge.......Page 2479
Rearward movement of the actin network in a growth-cone lamellipodium.......Page 2480
Lamellipodia and ruffles at the leading edge of a human fibroblast migrating in culture.......Page 2481
The localization of myosin I and myosin II in a normal crawling Dictyostelium amoeba.......Page 2482
Adhesive cells exert traction forces on the substratum.......Page 2483
Shaping of the extracellular matrix by cell pulling.......Page 2484
Neutrophil polarization and chemotaxis.......Page 2485
The polarization of a cytotoxic T cell after target-cell recognition.......Page 2486
Microtubule organization in fibroblasts and neurons.......Page 2487
Neuronal growth cones.......Page 2488
The complex architecture of a vertebrate neuron.......Page 2489
References......Page 2490
17. The Cell Cycle and Programmed Cell Death......Page 2495
The cell cycle.......Page 2497
An Overview of the Cell Cycle......Page 2498
The events of eucaryotic cell division as seen under a microscope.......Page 2504
The phases of the cell cycle.......Page 2505
A comparison of the cell cycles of fission yeasts and budding yeasts.......Page 2506
The behavior of a temperature-sensitive cdc mutant.......Page 2507
The morphology of budding yeast cells arrested by a cdc mutation.......Page 2508
A mature Xenopus egg, ready for fertilization.......Page 2509
Oocyte growth and egg cleavage in Xenopus.......Page 2510
Studying the cell cycle in a cell-free system.......Page 2511
Mammalian cells proliferating in culture.......Page 2512
Labeling S-phase cells.......Page 2513
Analysis of DNA content with a flow cytometer.......Page 2514
Components of the Cell-Cycle Control System......Page 2515
The control of the cell cycle.......Page 2522
Checkpoints in the cell-cycle control system.......Page 2523
Two key components of the cell-cycle control system.......Page 2524
A simplified view of the core of the cell-cycle control system.......Page 2525
The structural basis of Cdk activation.......Page 2526
The regulation of Cdk activity by inhibitory phosphorylation.......Page 2527
The inhibition of a cyclin-Cdk complex by a CKI.......Page 2528
The control of proteolysis by SCF and APC during the cell cycle.......Page 2529
The Major Cyclins and Cdks of Vertebrates and Budding Yeast......Page 2531
Intracellular Control of Cell-Cycle Events......Page 2532
Evidence from cell-fusion experiments for a rereplication block.......Page 2545
The initiation of DNA replication once per cell cycle.......Page 2546
The activation of M-Cdk.......Page 2548
The DNA replication checkpoint.......Page 2549
Two experiments that demonstrate the requirement for protein degradation to exit from mitosis.......Page 2550
The triggering of sister-chromatid separation by the APC.......Page 2551
Mad2 protein on unattached kinetochores.......Page 2552
The creation of a G 1 phase by stable Cdk inhibition after mitosis.......Page 2553
The control of G 1 progression by Cdk activity in budding yeast.......Page 2554
Mechanisms controlling S-phase initiation in animal cells.......Page 2555
Cell size control through control of the cell cycle in yeasts.......Page 2556
A hypothetical model of how budding yeast cells might coordinate cell growth and cell-cycle progression.......Page 2557
How DNA damage arrests the cell cycle in G 1 .......Page 2558
An overview of the cell-cycle control system.......Page 2560
Summary of the Major Cell-cycle Regulatory Proteins......Page 2561
Programmed Cell Death (Apoptosis)......Page 2563
Sculpting the digits in the developing mouse paw by apoptosis.......Page 2567
Apoptosis during the metamorphosis of a tadpole into a frog.......Page 2568
Cell death.......Page 2569
The caspase cascade involved in apoptosis.......Page 2571
Induction of apoptosis by either extracellular or intracellular stimuli.......Page 2573
Extracellular Control of Cell Division, Cell Growth, and Apoptosis......Page 2576
A platelet.......Page 2587
A simplified model of one way that mitogens stimulate cell division.......Page 2588
Cell-cycle arrest or apoptosis induced by excessive stimulation of mitogenic pathways.......Page 2590
Overcoming replicative cell senescence by the forced expression of telomerase.......Page 2591
One way in which growth factors promote cell growth.......Page 2592
The size difference between a neuron (from the retina) and a lymphocyte in a mammal.......Page 2593
The function of cell death in matching the number of developing nerve cells to the number of target cells they contact.......Page 2595
Two ways in which survival factors suppress apoptosis.......Page 2596
The effect of fresh medium on a confluent cell monolayer.......Page 2598
The dependence of cell division on cell shape and anchorage.......Page 2599
Focal adhesions as production sites of intracellular signals.......Page 2601
The effects of a myostatin mutation on muscle size.......Page 2602
Sections of kidney tubules from salamander larvae of different ploidies.......Page 2603
The hindbrain in a haploid and in a tetraploid salamander.......Page 2604
References......Page 2605
18. The Mechanics of Cell Division......Page 2609
The M phase of the cell cycle.......Page 2611
An Overview of M Phase......Page 2612
Human mitotic chromosomes stained to reveal a scaffold-like structure along the chromosome axis.......Page 2617
The related structure and function of cohesins and condensins.......Page 2618
Two cytoskeletal machines that operate in M phase.......Page 2619
Centrioles.......Page 2620
Centriole replication.......Page 2623
The centrosome cycle.......Page 2624
The course of mitosis in a typical animal cell.......Page 2626
The course of mitosis in a plant cell.......Page 2629
The Principal Stages of M Phase (Mitosis and Cytokinesis) in an Animal Cell......Page 2630
Mitosis......Page 2634
The three classes of microtubules of the fully formed mitotic spindle in an animal cell.......Page 2645
The half-life of microtubules in mitosis.......Page 2647
Experimental evidence that the balance between catastrophins and MAPs influences the frequency of microtubule catastrophes and microtubule length.......Page 2648
Two functions of multimeric motor proteins that are important for mitotic spindle assembly and function.......Page 2649
Separation of the two spindle poles in prophase in an animal cell.......Page 2650
The influence of opposing motor proteins on spindle length in budding yeast.......Page 2652
Kinetochore microtubules.......Page 2653
The capture of microtubules by kinetochores.......Page 2654
Chromosomes at the metaphase plate of a mitotic spindle.......Page 2655
The kinetochore.......Page 2656
The dynamic behavior of microtubules in the metaphase spindle studied by photoactivation of fluorescence.......Page 2657
Visualizing the dynamics of individual microtubules by fluorescence speckle microscopy.......Page 2659
How opposing forces may drive chromosomes to the metaphase plate.......Page 2660
Bipolar spindle assembly without centrosomes in parthenogenetic embryos of the insect Sciara.......Page 2661
Bipolar spindle assembly without centrosomes or kinetochores.......Page 2662
Chromatid separation at anaphase.......Page 2663
The major forces that separate daughter chromosomes at anaphase in mammalian cells.......Page 2664
Two alternative models of how the kinetochore may generate a poleward force on its chromosome during anaphase A.......Page 2666
The sliding of overlap microtubules at anaphase.......Page 2667
A model for how motor proteins may act in anaphase B.......Page 2668
Cytokinesis......Page 2669
Cleavage in a fertilized frog egg.......Page 2678
An experiment demonstrating the influence of the position of microtubule asters on the subsequent plane of cleavage in a large egg cell.......Page 2679
An asymmetric cell division segregating cytoplasmic components to only one daughter cell.......Page 2680
Spindle rotation.......Page 2681
The contractile ring.......Page 2682
The midbody.......Page 2683
Mitosis without cytokinesis in the Drosophila embryo.......Page 2685
Cytokinesis in a plant cell in telophase.......Page 2686
The special features of cytokinesis in a higher plant cell.......Page 2687
Cell division in the bacterium E. coli.......Page 2689
The FtsZ protein.......Page 2690
The use of different chromosome separation mechanisms by different organisms.......Page 2691
References......Page 2693
V. Cells in Their Social Context......Page 2698
19. Cell Junctions, Cell Adhesion, and the Extracellular Matrix......Page 2700
A cross-sectional view of part of the wall of the intestine.......Page 2702
The plant cell wall.......Page 2703
Cell Junctions......Page 2705
The role of tight junctions in transcellular transport.......Page 2716
The role of tight junctions in allowing epithelia to serve as barriers to solute diffusion.......Page 2718
The structure of a tight junction between epithelial cells of the small intestine.......Page 2719
A current model of a tight junction.......Page 2721
A septate junction.......Page 2722
Anchoring junctions in an epithelium.......Page 2723
The construction of an anchoring junction from two classes of proteins.......Page 2724
Adherens junctions.......Page 2725
The folding of an epithelial sheet to form an epithelial tube.......Page 2726
Desmosomes.......Page 2727
Focal adhesions.......Page 2729
Desmosomes and hemidesmosomes.......Page 2730
Determining the size of a gap-junction channel.......Page 2731
Gap junctions.......Page 2732
Gap junctions as seen in the electron microscope.......Page 2733
Gap junction coupling in the ovarian follicle.......Page 2734
The regulation of gap-junction coupling by a neurotransmitter.......Page 2735
A summary of the various cell junctions found in a vertebrate epithelial cell.......Page 2736
Plasmodesmata.......Page 2737
Various views of plasmodesmata.......Page 2738
A Functional Classification of Cell Junctions......Page 2740
Anchoring Junctions......Page 2741
Cell-Cell Adhesion......Page 2742
The simplest mechanism by which cells assemble to form a tissue.......Page 2752
An example of a more complex mechanism by which cells assemble to form a tissue.......Page 2753
The structure and function of cadherins.......Page 2755
The distribution of E-cadherin and N-cadherin in the developing nervous system.......Page 2756
Three mechanisms by which cell-surface molecules can mediate cell-cell adhesion.......Page 2757
Cadherin-dependent cell sorting.......Page 2758
Cadherin diversity in the central nervous system.......Page 2759
The linkage of classical cadherins to actin filaments.......Page 2760
The structure and function of selectins.......Page 2761
The cell adhesion protein N-CAM.......Page 2762
A summary of the junctional and nonjunctional adhesive mechanisms used by animal cells in binding to one another and to the extracellular matrix.......Page 2763
Some Members of the Cadherin Superfamily......Page 2765
The Extracellular Matrix of Animals......Page 2767
Cells surrounded by spaces filled with extracellular matrix.......Page 2788
The connective tissue underlying an epithelium.......Page 2789
Fibroblasts in connective tissue.......Page 2790
The repeating disaccharide sequence of a dermatan sulfate glycosaminoglycan (GAG) chain.......Page 2791
The relative dimensions and volumes occupied by various macromolecules.......Page 2792
The repeating disaccharide sequence in hyaluronan, a relatively simple GAG.......Page 2793
The linkage between a GAG chain and its core protein in a proteoglycan molecule.......Page 2794
Examples of a small (decorin) and a large (aggrecan) proteoglycan found in the extracellular matrix.......Page 2795
An aggrecan aggregate from fetal bovine cartilage.......Page 2796
Proteoglycans in the extracellular matrix of rat cartilage.......Page 2798
The structure of a typical collagen molecule.......Page 2799
Fibroblast surrounded by collagen fibrils in the connective tissue of embryonic chick skin.......Page 2801
Hydroxylysine and hydroxyproline.......Page 2802
Cross-links formed between modified lysine side chains within a collagen fibril.......Page 2803
The intracellular and extracellular events in the formation of a collagen fibril.......Page 2804
Collagen fibrils in the tadpole skin.......Page 2806
Type IX collagen.......Page 2807
The shaping of the extracellular matrix by cells.......Page 2808
Elastic fibers.......Page 2809
Stretching a network of elastin molecules.......Page 2810
The structure of a fibronectin dimer.......Page 2811
Coalignment of extracellular fibronectin fibrils and intracellular actin filament bundles.......Page 2812
Three ways in which basal laminae are organized.......Page 2813
The basal lamina in the cornea of a chick embryo.......Page 2814
The structure of laminin.......Page 2815
A model of the molecular structure of a basal lamina.......Page 2816
The comparative shapes and sizes of some of the major extracellular matrix macromolecules.......Page 2819
Regeneration experiments demonstrating the special character of the junctional basal lamina at a neuromuscular junction.......Page 2820
How the extracellular matrix could, in principle, propagate order from cell to cell within a tissue.......Page 2821
Anchorage dependence and the importance of cell spreading.......Page 2823
The importance of proteases bound to cell-surface receptors.......Page 2824
Some Common Proteoglycans......Page 2825
Some Types of Collagen and Their Properties......Page 2826
Integrins......Page 2828
The subunit structure of an integrin cell-surface matrix receptor.......Page 2834
The regulation of the extracellular binding activity of a cell\'s integrins from within.......Page 2836
Excessive numbers of focal adhesions in FAK-deficient fibroblasts.......Page 2837
Matrix-dependent cell survival in the formation of the proamniotic cavity.......Page 2838
Some Types of Integrins......Page 2839
Cell Adhesion Molecule Families......Page 2840
The Plant Cell Wall......Page 2841
Plant cell walls.......Page 2847
Specialized cell types with appropriately modified cell walls.......Page 2848
Cellulose.......Page 2849
Scale model of a portion of a primary cell wall showing the two major polysaccharide networks.......Page 2850
The orientation of cellulose microfibrils in the primary cell wall of an elongating carrot cell.......Page 2851
How the orientation of cellulose microfibrils within the cell wall influences the direction in which the cell elongates.......Page 2852
The cortical array of microtubules in a plant cell.......Page 2853
One model of how the orientation of newly deposited cellulose microfibrils might be determined by the orientation of cortical microtubules.......Page 2855
The Polymers of the Plant Cell Wall......Page 2856
References......Page 2857
20. Germ Cells and Fertilization......Page 2862
Human fertilization in vitro.......Page 2863
Photograph of a Hydra from which two new organisms are budding (arrows).......Page 2864
The Benefits of Sex......Page 2865
The sexual reproductive cycle.......Page 2868
Haploid and diploid cells in the life cycle of higher and some lower eucaryotes.......Page 2869
Scanning electron micrograph of a clam egg with sperm bound to its surface.......Page 2870
A peacock displaying his elaborate tail.......Page 2871
Meiosis......Page 2872
Events through the first cell division of meiosis.......Page 2882
Comparison of meiosis and mitotic cell division.......Page 2884
Two major contributions to the reassortment of genetic material that occurs in the production of gametes during meiosis.......Page 2886
Paired homologous chromosomes during the transition to metaphase of meiotic division I.......Page 2888
Bivalents with three chiasmata resulting from separate crossover events.......Page 2889
Comparison of the mechanisms of chromosome alignment (at metaphase) and separation (at anaphase) in meiotic division I and meiotic division II.......Page 2890
Chromosome synapsis and desynapsis during the different stages of meiotic prophase I.......Page 2892
A mature synaptonemal complex.......Page 2893
Comparison of the physical and genetic maps of part of chromosome I in budding yeast.......Page 2894
Comparison of times required for each of the stages of meiosis.......Page 2895
Primordial Germ Cells and Sex Determination in Mammals......Page 2897
Migration of mammalian primordial germ cells.......Page 2901
Sry- induced reprogramming of a female mouse embryo to develop into a male.......Page 2904
Influence of Sry on gonad development.......Page 2905
Eggs......Page 2907
The actual sizes of three eggs.......Page 2912
The relative sizes of various eggs.......Page 2913
The zona pellucida.......Page 2914
The stages of oogenesis.......Page 2915
Nurse cells and follicle cells associated with a Drosophila oocyte.......Page 2917
Electron micrographs of developing primary oocytes in the rabbit ovary.......Page 2918
Sperm......Page 2920
A human sperm.......Page 2923
Drawing of the midpiece of a mammalian sperm as seen in cross section in an electron microscope.......Page 2924
The stages of spermatogenesis.......Page 2925
Highly simplified drawing of a cross section of a seminiferous tubule in a mammalian testis.......Page 2927
Cytoplasmic bridges in developing sperm cells and their precursors.......Page 2928
Fertilization......Page 2930
Scanning electron micrograph of a human sperm contacting a hamster egg.......Page 2935
The acrosome reaction that occurs when a mammalian sperm fertilizes an egg.......Page 2936
How the cortical reaction in a mouse egg is thought to prevent additional sperm from entering the egg.......Page 2937
The fertilin protein in the sperm plasma membrane.......Page 2939
The coming together of the sperm and egg pronuclei after mammalian fertilization.......Page 2940
Immunofluorescence micrographs of human sperm and egg pronuclei coming together after in vitro fertilization.......Page 2941
References......Page 2943
21. Development of Multicellular Organisms......Page 2947
The four essential processes by which a multicellular organism is made: cell proliferation, cell specialization, cell interaction, and cell movement.......Page 2948
Universal Mechanisms of Animal Development......Page 2949
Homologous proteins functioning interchangeably in the development of mice and flies.......Page 2961
Sea urchin gastrulation.......Page 2963
How regulatory DNA defines the succession of gene expression patterns in development.......Page 2964
A cell lineage tracing experiment in the Xenopus embryo.......Page 2965
Some striking results obtained by experimental embryology.......Page 2966
The standard test for cell determination.......Page 2967
Prospective thigh tissue grafted into the tip of a chick wing bud forms toes.......Page 2968
Chick embryos at 4 days of incubation, showing the limb buds stained by in situ hybridization with probes to detect expression of the Tbx4 and Tbx5 genes.......Page 2969
Two ways of making sister cells different.......Page 2970
Lateral inhibition and cell diversification.......Page 2971
Inductive signaling.......Page 2972
Sonic hedgehog as a morphogen in chick limb development.......Page 2973
Two ways to create a morphogen gradient.......Page 2975
Patterning by sequential induction.......Page 2976
Some Signal Proteins That Are Used Over and Over Again as Inducers in Animal Development......Page 2977
Caenorhabditis Elegans: Development from the Perspective of the Individual Cell......Page 2978
Caenorhabditis elegans.......Page 2987
The lineage tree for the cells that form the gut (the intestine) of C. elegans.......Page 2988
Asymmetric divisions segregating P granules into the founder cell of the C. elegans germ line.......Page 2990
The pattern of cell divisions in the early nematode embryo, indicating the names and fates of the individual cells.......Page 2991
Cell-signaling pathways controlling assignment of different characters to the cells in a four-cell nematode embryo.......Page 2992
Heterochronic mutations in the lin-14 gene of C. elegans.......Page 2993
Apoptotic cell death in C. elegans.......Page 2995
Drosophila and the Molecular Genetics of Pattern Formation: Genesis of the Body Plan......Page 2997
Drosophila melanogaster.......Page 3009
Synopsis of Drosophila development from egg to adult fly.......Page 3010
The origins of the Drosophila body segments during embryonic development.......Page 3011
The segments of the Drosophila larva and their correspondence with regions of the blastoderm.......Page 3013
Development of the Drosophila egg from fertilization to the cellular blastoderm stage.......Page 3014
Fate map of a Drosophila embryo at the cellular blastoderm stage.......Page 3016
The domains of the anterior, posterior, and terminal systems of egg-polarity genes.......Page 3017
A Drosophila oocyte in its follicle.......Page 3019
The organization of the four egg-polarity gradient systems.......Page 3020
The concentration gradient of Dorsal protein in the nuclei of the blastoderm, as revealed by an antibody.......Page 3021
Morphogen gradients patterning the dorsoventral axis of the embryo.......Page 3022
Origin of the mesoderm from cells expressing twist.......Page 3024
The vertebrate body plan as a dorsoventral inversion of the insect body plan.......Page 3025
Examples of the phenotypes of mutations affecting the three types of segmentation genes.......Page 3026
The regulatory hierarchy of egg-polarity, gap, segmentation, and homeotic selector genes.......Page 3027
Modular organization of the regulatory DNA of the eve gene.......Page 3029
The formation of ftz and eve stripes in the Drosophila blastoderm.......Page 3030
The pattern of expression of engrailed, a segment-polarity gene.......Page 3031
Homeotic Selector Genes and the Patterning of the Anteroposterior Axis......Page 3032
A homeotic mutation.......Page 3038
The effect of deleting most of the genes of the bithorax complex.......Page 3039
The patterns of expression compared to the chromosomal locations of the genes of the Hox complex.......Page 3040
Action of genes of the Polycomb group.......Page 3042
The Hox complex of an insect and the Hox complexes of a mammal compared and related to body regions.......Page 3044
Expression domains of Hox genes in a mouse.......Page 3046
Segmentation and Hox gene expression in the hindbrain, as seen in a chick embryo.......Page 3048
Organogenesis and the Patterning of Appendages......Page 3050
Creation of mutant cells by induced somatic recombination.......Page 3063
The GAL4/UAS technique for controlled gene misexpression in Drosophila.......Page 3065
The imaginal discs in the Drosophila larva and the adult structures they give rise to.......Page 3067
Expression of Distal-less in developing legs and related appendages of various species.......Page 3068
Gene expression domains in the wing imaginal disc, defining quadrants of the future wing.......Page 3069
Compartments in the adult wing.......Page 3071
Morphogenetic signals created at compartment boundaries in the wing imaginal disc.......Page 3073
Intercalary regeneration.......Page 3074
Molecules that control patterning in a vertebrate limb bud.......Page 3075
The basic structure of a mechanosensory bristle.......Page 3076
Sensory mother cells in the wing imaginal disc.......Page 3077
Lateral inhibition.......Page 3078
The result of switching off lateral inhibition during the singling-out of sensory mother cells.......Page 3080
Numb biases lateral inhibition during bristle development.......Page 3081
Planar cell polarity manifest in bristle polarity on a fly\'s back: the bristles all point backwards.......Page 3082
The control of planar cell polarity.......Page 3083
Effects of blocking Notch signaling in a Xenopus embryo.......Page 3084
Cell Movements and the Shaping of the Vertebrate Body......Page 3085
Synopsis of the development of Xenopus laevis from newly fertilized egg to feeding tadpole.......Page 3097
The Xenopus egg and its asymmetries.......Page 3099
The stages of cleavage in Xenopus.......Page 3100
The origins of the three germ layers can be traced back to distinct blastomeres of the embryo in its early cleavage stages.......Page 3101
The blastula.......Page 3102
A cross section through the trunk of an amphibian embryo after the end of gastrulation, showing the arrangement of endodermal, mesodermal and ectodermal tissues.......Page 3103
Gastrulation in Xenopus.......Page 3104
A current view of the main inductive signals organizing the events of gastrulation.......Page 3106
Cell movements in gastrulation.......Page 3107
Convergent extension and its cellular basis.......Page 3108
Sorting out.......Page 3109
Neural tube formation in Xenopus.......Page 3111
The bending of an epithelium through cell shape changes mediated by microtubules and actin filaments.......Page 3112
Somite formation in the chick embryo.......Page 3113
The migratory origin of limb muscle cells.......Page 3114
The main pathways of neural crest cell migration.......Page 3116
Effect of mutations in the kit gene.......Page 3117
Helical beating of cilia at the node, and the origins of left-right asymmetry.......Page 3118
The Mouse......Page 3120
The early stages of mouse development.......Page 3126
Scanning electron micrographs of the early mouse embryo.......Page 3127
A procedure for creating a chimeric mouse.......Page 3128
Making a chimeric mouse with ES cells.......Page 3130
Branching morphogenesis of the lung.......Page 3131
Neural Development......Page 3132
A typical neuron of a vertebrate.......Page 3145
The complex organization of nerve cell connections.......Page 3146
The three phases of neural development.......Page 3147
Diagram of a 2-day chick embryo, showing the origins of the nervous system.......Page 3148
Formation of the neural tube.......Page 3149
Migration of immature neurons.......Page 3150
A schematic cross section of the spinal cord of a chick embryo, showing how cells at different levels along the dorsoventral axis express different gene regulatory proteins.......Page 3152
Programmed production of different types of neurons at different times from dividing progenitors in the cerebral cortex of the brain of a mammal.......Page 3153
Growing axons in the developing spinal cord of a 3-day chick embryo.......Page 3154
Formation of axon and dendrites in culture.......Page 3155
The guidance of commissural axons.......Page 3156
NGF effects on neurite outgrowth.......Page 3157
The neural map from eye to brain in a young zebrafish.......Page 3159
A map of the body surface in the human brain.......Page 3160
Selectivity of retinal axons growing over tectal membranes.......Page 3161
Sharpening of the retinotectal map by synapse elimination.......Page 3162
Synapse modification and its dependence on electrical activity.......Page 3164
Ocular dominance columns in the visual cortex of a monkey\'s brain, and their sensitivity to visual experience.......Page 3165
Plant Development......Page 3166
A simple example of the modular construction of plants.......Page 3178
Arabidopsis thaliana.......Page 3179
Production of mutants in Arabidopsis.......Page 3180
Two stages of embryogenesis in Arabidopsis thaliana.......Page 3181
Mutant Arabidopsis seedlings.......Page 3182
A seedling of Arabidopsis.......Page 3183
A growing root tip.......Page 3184
The different effects of the plant growth regulators ethylene and gibberellic acid.......Page 3185
Repetitive patterning in plants.......Page 3186
A shoot apex from a young tobacco plant.......Page 3187
The feedback loops that are thought to maintain the shoot apical meristem.......Page 3188
Axillary buds in the neighborhood of a shoot apex.......Page 3189
Transformation of plant architecture by mutation: a comparison of teosinte, normal maize, and tb1 -defective maize.......Page 3190
Plant growth regulators.......Page 3192
The structure of an Arabidopsis flower.......Page 3193
Arabidopsis flowers showing a selection of homeotic mutations.......Page 3194
Homeotic selector gene expression in an Arabidopsis flower.......Page 3196
Some Major Families of Gene Regulatory Proteins in Arabidopsis, Drosophila, C. elegans, and the Yeast Saccharomyces cerevisiae......Page 3198
Features of Early Development in Flowering Plants......Page 3200
The Cell Types and Tissues From Which Higher Plants Are Constructed......Page 3202
References......Page 3206
22. Histology: The Lives and Deaths of Cells in Tissues......Page 3211
Epidermis and Its Renewal by Stem Cells......Page 3212
Mammalian skin.......Page 3220
The multilayered structure of the epidermis, as seen in a mouse.......Page 3222
A prickle cell.......Page 3223
The definition of a stem cell.......Page 3224
Two ways for a stem cell to produce daughters with different fates.......Page 3225
The distribution of stem cells in human epidermis, and the pattern of epidermal cell production.......Page 3226
Transit amplifying cells.......Page 3227
The mammary gland.......Page 3228
Death of milk-secreting cells when suckling stops.......Page 3230
Sensory Epithelia......Page 3232
Olfactory epithelium and olfactory neurons.......Page 3236
Auditory hair cells.......Page 3237
How a relative movement of the overlying extracellular matrix (the tectorial membrane) tilts the stereocilia of auditory hair cells in the organ of Corti in the inner ear of a mammal.......Page 3238
How a sensory hair cell works.......Page 3239
The structure of the retina.......Page 3240
A rod photoreceptor.......Page 3241
Turnover of membrane protein in a rod cell.......Page 3242
The Airways and the Gut......Page 3243
Alveoli in the lung.......Page 3250
Respiratory epithelium.......Page 3251
Renewal of the gut lining.......Page 3252
The four main differentiated cell types found in the epithelial lining of the small intestine.......Page 3253
The structure of the liver.......Page 3255
Blood Vessels and Endothelial Cells......Page 3256
Diagram of a small artery in cross section.......Page 3261
Capillaries.......Page 3262
Pericytes.......Page 3263
Angiogenesis.......Page 3264
Capillary formation in vitro.......Page 3265
New capillary formation in response to wounding.......Page 3266
The regulatory mechanism controlling blood vessel growth according to a tissue\'s need for oxygen.......Page 3267
Renewal by Multipotent Stem Cells: Blood Cell Formation......Page 3268
Scanning electron micrograph of mammalian blood cells caught in a blood clot.......Page 3280
White blood cells.......Page 3281
The migration of white blood cells out of the bloodstream during an inflammatory response.......Page 3283
Bone marrow.......Page 3285
A megakaryocyte among other cells in the bone marrow.......Page 3286
Rescue of an irradiated mouse by a transfusion of bone marrow cells.......Page 3287
A tentative scheme of hemopoiesis.......Page 3288
Dependence of hemopoietic stem cells on contact with stromal cells.......Page 3290
A developing red blood cell (erythroblast).......Page 3291
Sharing of subunits among CSF receptors.......Page 3292
Some of the parameters through which the production of blood cells of a specific type might be regulated.......Page 3293
Blood Cells......Page 3294
Some Colony-stimulating Factors (CSFs) That Influence Blood Cell Formation......Page 3296
Genesis, Modulation, and Regeneration of Skeletal Muscle......Page 3297
The four classes of muscle cells of a mammal.......Page 3302
Myoblast fusion in culture.......Page 3305
Fast and slow muscle fibers.......Page 3307
Regulation of muscle size by myostatin.......Page 3308
A satellite cell on a skeletal muscle fiber.......Page 3309
Fibroblasts and Their Transformations: The Connective-Tissue Cell Family......Page 3310
The family of connective-tissue cells.......Page 3318
The fibroblast.......Page 3319
The development of a fat cell.......Page 3321
Fat cells.......Page 3322
Effects of leptin deficiency.......Page 3323
Achondroplasia.......Page 3324
The growth of cartilage.......Page 3325
Deposition of bone matrix by osteoblasts.......Page 3326
An osteoclast shown in cross section.......Page 3327
The remodeling of compact bone.......Page 3328
A transverse section through a compact outer portion of a long bone.......Page 3329
The development of a long bone.......Page 3330
Stem-Cell Engineering......Page 3331
Production of differentiated cells from mouse ES cells in culture.......Page 3336
The continuing production of neurons in an adult mouse brain.......Page 3338
References......Page 3339
23. Cancer......Page 3344
Cancer as a Microevolutionary Process......Page 3345
Metastasis.......Page 3358
Cancer incidence and mortality in the United States.......Page 3359
Benign versus malignant tumors.......Page 3360
The growth of a typical human tumor such as a tumor of the breast.......Page 3361
The translocation between chromosomes 9 and 22 responsible for chronic myelogenous leukemia.......Page 3362
Evidence from X-inactivation mosaics demonstrates the monoclonal origin of cancers.......Page 3363
Cancer incidence as a function of age.......Page 3364
Delayed onset of cancer following exposure to a carcinogen.......Page 3365
The stages of progression in the development of cancer of the epithelium of the uterine cervix.......Page 3366
Photographs of cells collected by scraping the surface of the uterine cervix (the Papanicolaou or Pap smear technique).......Page 3367
Clonal evolution.......Page 3368
Chromosomes from a breast tumor displaying abnormalities in structure and number.......Page 3369
Genetic instability and tumor progression.......Page 3370
Normal and deranged control of cell production from stem cells.......Page 3371
Steps in the process of metastasis.......Page 3372
Colon cancer invading the smooth muscle layer that lies beneath the colon epithelium.......Page 3375
The Preventable Causes of Cancer......Page 3376
The Ames test for mutagenicity.......Page 3382
Metabolic activation of a carcinogen.......Page 3383
Some possible schedules of exposure to a tumor initiator (mutagenic) and a tumor promoter (nonmutagenic) and their outcomes.......Page 3384
The effect of a tumor promoter.......Page 3385
A human papillomavirus.......Page 3386
Age-adjusted cancer death rates, United States, 1930-1996.......Page 3387
Effects of childbearing on the risk of breast cancer.......Page 3388
Variation Between Countries in the Incidence of Some Common Cancers......Page 3389
Viruses Associated with Human Cancers......Page 3391
Finding the Cancer-Critical Genes......Page 3393
Cancer-critical genes fall into two readily distinguishable categories, dominant and recessive.......Page 3402
Loss of contact inhibition in cell culture.......Page 3403
The genetic mechanisms underlying retinoblastoma.......Page 3404
Three ways in which a proto-oncogene can be made overactive to convert it into an oncogene.......Page 3405
Chromosomal changes in cancer cells reflecting gene amplification.......Page 3406
Six ways of losing the remaining good copy of a tumor suppressor gene.......Page 3407
The Molecular Basis of Cancer-Cell Behavior......Page 3408
Oncogene collaboration in transgenic mice.......Page 3425
Chart of the major signaling pathways relevant to cancer in human cells, indicating the cellular locations of some of the proteins modified by mutation in cancers.......Page 3426
The pathway that controls cell cycling via Rb protein.......Page 3428
How the replication of damaged DNA can lead to chromosome abnormalities, gene amplification and gene loss.......Page 3429
How certain papillomaviruses are thought to give rise to cancer of the uterine cervix.......Page 3430
Activation of cell proliferation by a DNA tumor virus.......Page 3431
A view of how shortened telomeres may lead to chromosomal instability and cancer.......Page 3432
The barriers to metastasis.......Page 3434
Cross-sections showing the stages in development of a typical colon cancer.......Page 3435
Colon of familial adenomatous polyposis coli patient compared to normal colon.......Page 3437
Chromosome complements (karyotypes) of colon cancers showing different kinds of genetic instability.......Page 3438
Suggested typical sequence of genetic changes underlying the development of a colorectal carcinoma.......Page 3439
Each tumor will generally contain a different set of genetic lesions.......Page 3440
Some Genetic Abnormalities Detected in Colorectal Cancer Cells......Page 3441
Cancer Treatment: Present and Future......Page 3442
Effects of ionizing radiation on normal cells (A) and cancer cells (B).......Page 3449
The conversion of the Abl proto-oncogene into an oncogene in patients with chronic myelogenous leukemia.......Page 3450
How Gleevec (STI-571) blocks the activity of Bcr-Abl protein and halts chronic myeloid leukemia.......Page 3451
References......Page 3453
24. The Adaptive Immune System......Page 3457
Lymphocytes and the Cellular Basis of Adaptive Immunity......Page 3460
Human lymphoid organs.......Page 3470
A classic experiment showing that lymphocytes are required for adaptive immune responses to foreign antigens.......Page 3471
One way in which the innate immune system helps activate the adaptive immune system.......Page 3472
The development and activation of T and B cells.......Page 3474
Electron micrographs of nonactivated and activated lymphocytes.......Page 3475
The clonal selection theory.......Page 3477
The dinitrophenyl (DNP) group.......Page 3478
Primary and secondary antibody responses.......Page 3479
A model for the cellular basis of immunological memory.......Page 3480
Immunological tolerance.......Page 3481
Induction of immunological tolerance to self antigens in central and peripheral lymphoid organs.......Page 3482
The path followed by lymphocytes as they continuously circulate between the lymph and blood.......Page 3483
Migration of a lymphocyte out of the bloodstream into a lymph node.......Page 3484
A simplified drawing of a human lymph node.......Page 3485
B Cells and Antibodies......Page 3486
B cell activation.......Page 3495
A simple representation of an antibody molecule.......Page 3496
Antibody-antigen interactions.......Page 3497
The hinge region of an antibody molecule.......Page 3498
A schematic drawing of a typical antibody molecule.......Page 3499
The main stages in B cell development.......Page 3500
A pentameric IgM molecule.......Page 3501
Antibody-activated phagocytosis.......Page 3502
A highly schematized diagram of a dimeric IgA molecule found in secretions.......Page 3503
The mechanism of transport of a dimeric IgA molecule across an epithelial cell.......Page 3504
The role of IgE in histamine secretion by mast cells.......Page 3505
Antigen binding to antibody.......Page 3506
Molecules with multiple antigenic determinants.......Page 3507
Constant and variable regions of immunoglobulin chains.......Page 3508
Antibody hypervariable regions.......Page 3509
Immunoglobulin domains.......Page 3510
The organization of the DNA sequences that encode the constant region of an antibody heavy chain.......Page 3511
The folded structure of an IgG antibody molecule, based on x-ray crystallography studies.......Page 3512
Antigen-binding sites of antibodies.......Page 3513
Properties of the Major Classes of Antibodies in Humans......Page 3514
The Generation of Antibody Diversity......Page 3515
Drawing of an experiment that directly demonstrates that DNA is rearranged during B cell development.......Page 3523
The V-J joining process involved in making a human light chain.......Page 3524
The human heavy-chain gene-segment pool.......Page 3526
The four main mechanisms of antibody diversification.......Page 3527
Antibody gene-pool selection in B cell development.......Page 3528
An example of the DNA rearrangement that occurs in class switch recombination.......Page 3530
T Cells and MHC Proteins......Page 3531
A T cell receptor heterodimer.......Page 3548
Immunofluorescence micrograph of a dendritic cell in culture.......Page 3549
Three types of proteins on the surface of an antigen-presenting cell involved in activating a T cell.......Page 3550
Effector cytotoxic T cells killing target cells in culture.......Page 3551
Two strategies by which effector cytotoxic T cells kill their target cells.......Page 3553
Differentiation of na ve helper T cells into either T H 1 or T H 2 effector helper cells in a peripheral lymphoid organ.......Page 3554
Recognition by T cells of foreign peptides bound to MHC proteins.......Page 3555
Class I and class II MHC proteins.......Page 3556
Human MHC genes.......Page 3557
The three-dimensional structure of a human class I MHC protein as determined by x-ray diffraction analysis of crystals of the extracellular part of the molecule.......Page 3558
A peptide bound in the groove of a class I MHC protein.......Page 3560
A peptide bound in the groove of a class II MHC protein.......Page 3561
The interaction of a T cell receptor with a viral peptide bound to a class I MHC protein.......Page 3562
CD4 and CD8 co-receptors on the surface of T cells.......Page 3563
The classic experiment showing that an effector cytotoxic T cell recognizes some aspect of the surface of the host target cell in addition to a viral antigen.......Page 3564
The peptide-transport problem.......Page 3565
The processing of a viral protein for presentation to cytotoxic T cells.......Page 3566
Some effects of interferon- on infected cells.......Page 3567
The processing of an extracellular protein antigen for presentation to a helper T cell.......Page 3568
Positive and negative selection in the thymus.......Page 3570
Properties of Human Class I and Class II MHC Proteins......Page 3571
Helper T Cells and Lymphocyte Activation......Page 3572
The two signals that activate a helper T cell.......Page 3582
The T cell receptor and its associated CD3 complex.......Page 3583
The signaling events initiated by the binding of peptide-MHC complexes to T cell receptors (signal 1).......Page 3584
The stimulation of T cells by IL-2 in culture.......Page 3585
The activation of T H 1 and T H 2 cells.......Page 3586
The differentiation of T H 1 cells and their activation of macrophages.......Page 3587
Signaling events activated by the binding of antigen to B cell receptors (signal I).......Page 3588
The influence of B cell co-receptors on the effectiveness of signal I.......Page 3589
Comparison of the signals required to activate a helper T cell and a B cell.......Page 3590
Some of the membrane proteins belonging to the Ig superfamily.......Page 3591
Some Accessory Proteins on the Surface of T Cells......Page 3592
Properties of Some Interleukins......Page 3594
References......Page 3596
25. Pathogens, Infection, and Innate Immunity......Page 3601
Host-pathogen interactions.......Page 3603
Introduction to Pathogens......Page 3605
Parasitism at many levels.......Page 3614
Pathogens in many forms.......Page 3615
Phylogenetic diversity of pathogens.......Page 3616
Bacterial shapes and cell-surface structures.......Page 3617
Genetic differences between pathogens and nonpathogens.......Page 3620
Genetic organization of Vibrio cholerae .......Page 3621
Type III secretion systems that can deliver virulence factors into the cytoplasm of host cells.......Page 3622
Antibiotic targets.......Page 3623
Dimorphism in the pathogenic fungus Histoplasma capsulatum .......Page 3624
The complex life cycle of malaria.......Page 3625
A simple viral life cycle.......Page 3627
Examples of viral morphology.......Page 3628
Schematic drawings of several types of viral genomes.......Page 3629
Acquisition of a viral envelope.......Page 3630
A map of the HIV genome.......Page 3631
Eradication of a viral disease through vaccination.......Page 3632
Neural degeneration in a prion infection.......Page 3633
Cell Biology of Infection......Page 3634
The spread of plague.......Page 3652
Uropathogenic E. coli and P pili.......Page 3653
Interaction of enteropathogenic E. coli (EPEC) with host cells.......Page 3654
Receptor and co-receptors for HIV.......Page 3656
Four virus uncoating strategies.......Page 3657
The entry strategy used by the influenza virus.......Page 3659
Uptake of Legionella pneumophila by a human mononuclear phagocyte.......Page 3660
Mechanisms used by bacteria to induce phagocytosis by nonphagocytic host cells.......Page 3661
The life cycle of the intracellular parasite Toxoplasma gondii .......Page 3662
Invasion of Trypansoma cruzi......Page 3663
The choices faced by an intracellular pathogen.......Page 3664
Selective destruction of the phagosomal membrane by Listeria monocytogenes .......Page 3665
Modifications of intracellular membrane trafficking by bacterial pathogens.......Page 3666
Complicated strategies for viral envelope acquisition.......Page 3667
Intracellular membrane alterations induced by a poliovirus protein.......Page 3669
The actin-based movement of Listeria monocytogenes within and between host cells.......Page 3670
Molecular mechanisms for actin nucleation by various pathogens.......Page 3671
Trafficking of herpes virus in an axon.......Page 3672
Wolbachia associates with microtubules.......Page 3673
Antigenic variation in trypanosomes.......Page 3674
Diversification of HIV-1, HIV-2, and related strains of SIV.......Page 3675
Innate Immunity......Page 3676
Epithelial defenses against microbial invasion.......Page 3687
Structure of lipopolysaccharide (LPS).......Page 3688
The principal stages in complement activation by the classical, lectin, and alternative pathways.......Page 3690
Assembly of the late complement components to form a membrane attack complex.......Page 3691
Electron micrographs of negatively stained complement lesions in the plasma membrane of a red blood cell.......Page 3692
The activation of a macrophage by lipopolysaccharide (LPS).......Page 3693
Microbial disease in a plant.......Page 3695
Phagocytosis.......Page 3696
Eosinophils attacking a schistosome larva.......Page 3697
Inflammation of the airways in chronic asthma restricts breathing.......Page 3698
A natural killer (NK) cell attacking a cancer cell.......Page 3699
References......Page 3700
Glossary......Page 3705