The Cell: A Molecular Approach

Cover......Page 1
The Cell: A Molecular Approach......Page 2
Brief Table of Contents......Page 6
Contents......Page 8
About the Author......Page 18
Preface......Page 20
PART I: Fundamentals and Foundations......Page 30
CHAPTER 1: Introduction to Cells and Cell Research......Page 32
How did the first cell arise?......Page 33
The evolution of metabolism......Page 36
Prokaryotes......Page 37
Eukaryotic cells......Page 38
The origin of eukaryotes......Page 40
The development of multicellular organisms......Page 42
E. coli......Page 47
Yeasts......Page 48
Caenorhabditis elegans and Drosophila melanogaster......Page 49
Vertebrates......Page 50
Animal cell culture......Page 52
Viruses......Page 53
Key Experiment HeLa Cells: The First Human Cell Line......Page 54
Molecular Medicine: Viruses and Cancer......Page 55
Light microscopy......Page 57
Fluorescence microscopy and GFP......Page 60
Following protein movements and interactions......Page 61
Sharpening the focus and seeing cells in three dimensions......Page 62
Super-resolution microscopy: breaking the diffraction barrier......Page 63
Electron microscopy......Page 65
Subcellular fractionation......Page 66
Data Analysis Problems......Page 71
Animations and Videos......Page 72
2.1 The Molecules of Cells......Page 74
Chemical bonds......Page 75
Carbohydrates......Page 78
Lipids......Page 80
Nucleic acids......Page 82
Proteins......Page 84
Key Experiment The Folding of Polypeptide Chains......Page 87
The catalytic activity of enzymes......Page 92
Mechanisms of enzymatic catalysis......Page 93
Coenzymes......Page 95
Regulation of enzyme activity......Page 96
Membrane lipids......Page 100
Membrane proteins......Page 102
Key Experiment The Structure of Cell Membranes......Page 103
Transport across cell membranes......Page 104
Data Analysis Problems......Page 107
Animations and Videos......Page 109
The laws of thermodynamics......Page 110
The role of ATP......Page 112
3.2 Glycolysis and Oxidative Phosphorylation......Page 114
Glycolysis......Page 115
The citric acid cycle......Page 117
Electron transport and oxidative phosphorylation......Page 119
Chemiosmotic coupling......Page 122
Key Experiment The Chemiosmotic Theory......Page 123
Electron transport......Page 126
ATP synthesis......Page 129
Synthesis of glucose......Page 130
3.4 The Biosynthesis of Cell Constituents......Page 131
Carbohydrates......Page 132
Proteins......Page 133
Key Experiment Antimetabolites, Cancer, and AIDS......Page 136
Nucleic acids......Page 137
Data Analysis Problems......Page 138
Animations and Videos......Page 140
4.1 Heredity, Genes, and DNA......Page 142
Genes and chromosomes......Page 143
The structure of DNA......Page 146
Replication of DNA......Page 148
The role of messenger RNA......Page 151
The genetic code......Page 152
RNA viruses and reverse transcription......Page 154
Key Experiment The DNA Provirus Hypothesis......Page 156
4.3 Recombinant DNA......Page 157
Restriction endonucleases......Page 158
Generation of recombinant DNA molecules......Page 160
DNA sequencing......Page 162
Expression of cloned genes......Page 163
Amplification of DNA by the polymerase chain reaction......Page 166
Nucleic acid hybridization......Page 168
Antibodies as probes for proteins......Page 170
4.5 Gene Function in Eukaryotes......Page 172
Gene transfer in plants and animals......Page 173
Mutagenesis of cloned DNAs......Page 175
Introducing mutations into cellular genes......Page 177
Genome engineering by the CRISPR/Cas system......Page 178
Targeting mRNA......Page 179
Key Experiment RNA Interference......Page 181
Data Analysis Problems......Page 183
Suggested Reading......Page 184
Animations and Videos......Page 185
5.1 Genomes and Transcriptomes......Page 186
The genomes of bacteria and yeast......Page 187
The genomes of Caenorhabditis elegans, Drosophila melanogaster, and Arabidopsis thaliana......Page 188
The human genome......Page 189
The genomes of other vertebrates......Page 190
Key Experiment The Human Genome......Page 192
Next-generation sequencing and personal genomes......Page 193
Global analysis of gene expression......Page 195
5.2 Proteomics......Page 197
Identification of cell proteins......Page 198
Global analysis of protein localization......Page 199
Protein interactions......Page 200
5.3 Systems Biology......Page 203
Systematic screens of gene function......Page 204
Regulation of gene expression......Page 205
Networks......Page 206
Synthetic biology......Page 208
Molecular Medicine Malaria and Synthetic Biology......Page 210
Data Analysis Problem......Page 212
Animations and Videos......Page 213
PART II: The Flow of Genetic Information......Page 214
6.1 The Structure of Eukaryotic Genes......Page 216
Introns and exons......Page 218
Key Experiment The Discovery of Introns......Page 220
Roles of introns......Page 222
6.2 Noncoding Sequences......Page 224
Noncoding RNAs......Page 225
Key Experiment The ENCODE Project......Page 226
Repetitive sequences......Page 227
Gene duplication and pseudogenes......Page 230
6.3 Chromosomes and Chromatin......Page 234
Chromatin......Page 235
Centromeres......Page 238
Telomeres......Page 241
Data Analysis Problems......Page 242
Animations and Videos......Page 243
7.1 DNA Replication......Page 244
The replication fork......Page 245
The fidelity of replication......Page 253
Origins and the initiation of replication......Page 254
Telomeres and telomerase: Maintaining the ends of chromosomes......Page 257
Key Experiment Telomerase Is a Reverse Transcriptase......Page 258
Direct reversal of DNA damage......Page 261
Excision repair......Page 263
Molecular Medicine Colon Cancer and DNA Repair......Page 267
Translesion DNA synthesis......Page 268
Repair of double-strand breaks......Page 269
7.3 DNA Rearrangements and Gene Amplification......Page 271
Antibody genes......Page 272
Gene amplification......Page 277
Data Analysis Problems......Page 279
Suggested Reading......Page 280
Animations and Videos......Page 281
8.1 Transcription in Bacteria......Page 282
Bacterial promoters......Page 283
Elongation and termination......Page 284
8.2 Eukaryotic RNA Polymerases and General Transcription Factors......Page 287
General transcription factors and initiation of transcription by RNA polymerase II......Page 288
Transcription by RNA polymerases I and III......Page 292
8.3 RNA Processing and Turnover......Page 294
Processing of ribosomal and transfer RNAs......Page 295
Processing of mRNA in eukaryotes......Page 296
Splicing mechanisms......Page 299
Key Experiment The Discovery of snRNPs......Page 303
Alternative splicing......Page 305
Molecular Medicine Splicing Therapy for Duchenne Muscular Dystrophy......Page 307
RNA editing......Page 308
RNA degradation......Page 309
Data Analysis Problems......Page 311
Animations and Videos......Page 313
The lac repressor......Page 314
Positive control of transcription......Page 316
cis-acting regulatory sequences: promoters and enhancers......Page 317
Transcription factor binding sites......Page 321
Transcriptional regulatory proteins......Page 324
Key Experiment Isolation of a Eukaryotic Transcription Factor......Page 325
Regulation of elongation......Page 327
Histone modifications......Page 330
Key Experiment The Role of Histone Modification......Page 332
Chromatin remodeling factors......Page 335
Histones and epigenetic inheritance......Page 336
DNA methylation......Page 337
Noncoding RNAs......Page 339
Data Analysis Problem......Page 341
Animations and Videos......Page 342
10.1 Translation of mRNA......Page 344
Transfer RNAs......Page 345
The ribosome......Page 347
The organization of mRNAs and the initiation of translation......Page 349
The process of translation......Page 351
Regulation of translation......Page 355
Chaperones and protein folding......Page 360
Protein misfolding diseases......Page 363
Molecular Medicine Alzheimer’s Disease......Page 365
Protein cleavage......Page 366
Attachment of carbohydrates and lipids......Page 367
Regulation by small molecules......Page 370
Protein phosphorylation and other modifications......Page 371
Key Experiment The Discovery of Tyrosine Kinases......Page 374
Protein–protein interactions......Page 375
Protein degradation......Page 376
Data Analysis Problems......Page 378
Suggested Reading......Page 379
Animations and Videos......Page 380
PART III: Cell Structure and Function......Page 382
11.1 The Nuclear Envelope and Traffic between the Nucleus and the Cytoplasm......Page 384
Structure of the nuclear envelope......Page 385
The nuclear pore complex......Page 387
Molecular Medicine Nuclear Lamina Diseases......Page 388
Selective transport of proteins to and from the nucleus......Page 391
Key Experiment Identification of Nuclear Localization Signals......Page 392
Transport of RNAs......Page 395
Regulation of nuclear protein import......Page 396
11.2 The Organization of Chromatin......Page 398
Chromosome territories......Page 399
Chromatin localization and transcriptional activity......Page 400
Replication and transcription factories......Page 402
11.3 Nuclear Bodies......Page 404
The nucleolus and rRNA......Page 405
Polycomb bodies: Centers of transcriptional repression......Page 407
Cajal bodies and speckles: Processing and storage of snRNPs......Page 408
Data Analysis Problems......Page 409
Animations and Videos......Page 411
12.1 The Endoplasmic Reticulum......Page 412
The endoplasmic reticulum and protein secretion......Page 413
Targeting proteins to the endoplasmic reticulum......Page 414
Key Experiment The Signal Hypothesis......Page 416
Insertion of proteins into the ER membrane......Page 419
Protein folding and processing in the ER......Page 424
Quality control in the ER......Page 427
The smooth ER and lipid synthesis......Page 429
Export of proteins and lipids from the ER......Page 431
12.2 The Golgi Apparatus......Page 433
Organization of the Golgi......Page 434
Protein glycosylation within the Golgi......Page 435
Lipid and polysaccharide metabolism in the Golgi......Page 436
Protein sorting and export from the Golgi apparatus......Page 438
Cargo selection, coat proteins, and vesicle budding......Page 441
Vesicle fusion......Page 444
Lysosomal acid hydrolases......Page 446
Molecular Medicine Gaucher Disease......Page 447
Autophagy......Page 448
Data Analysis Problems......Page 451
Suggested Reading......Page 452
Animations and Videos......Page 453
13.1 Mitochondria......Page 454
Organization and function of mitochondria......Page 455
The genetic system of mitochondria......Page 457
Molecular Medicine Mitochondrial Replacement Therapy......Page 459
Mitochondrial lipids......Page 463
Transport of metabolites across the inner membrane......Page 464
13.2 Chloroplasts and Other Plastids......Page 466
The structure and function of chloroplasts......Page 467
Import and sorting of chloroplast proteins......Page 469
Other plastids......Page 471
Functions of peroxisomes......Page 474
Peroxisome assembly......Page 475
Molecular Medicine Peroxisome Biogenesis Disorders......Page 476
Data Analysis Problems......Page 479
Animations and Videos......Page 480
14.1 Structure and Organization of Actin Filaments......Page 482
Assembly and organization of actin filaments......Page 483
Association of actin filaments with the plasma membrane......Page 487
Microvilli......Page 490
Cell surface protrusions and cell movement......Page 491
14.2 Myosin Motors......Page 494
Muscle contraction......Page 495
Contractile assemblies of actin and myosin in nonmuscle cells......Page 499
Unconventional myosins......Page 500
14.3 Microtubules......Page 501
Structure and dynamic organization of microtubules......Page 502
Assembly of microtubules......Page 505
MAPs and the organization of microtubules......Page 506
14.4 Microtubule Motors and Movement......Page 508
Key Experiment The Isolation of Kinesin......Page 509
Microtubule motor proteins......Page 510
Cargo transport and intracellular organization......Page 512
Cilia and flagella......Page 513
Microtubules during mitosis......Page 516
Intermediate filament proteins......Page 519
Assembly of intermediate filaments......Page 520
Intracellular organization of intermediate filaments......Page 521
Key Experiment Function of Intermediate Filaments......Page 524
Data Analysis Problems......Page 526
Suggested Reading......Page 527
Animations and Videos......Page 528
The lipid bilayer......Page 530
Plasma membrane proteins......Page 534
Plasma membrane domains......Page 539
Facilitated diffusion and carrier proteins......Page 543
Ion channels......Page 545
Active transport driven by ATP hydrolysis......Page 550
Molecular Medicine Cystic Fibrosis......Page 554
Phagocytosis......Page 557
Clathrin-mediated endocytosis......Page 558
Key Experiment The LDL Receptor......Page 560
Transport to lysosomes and receptor recycling......Page 562
Data Analysis Problems......Page 564
Animations and Videos......Page 566
Bacterial cell walls......Page 568
Eukaryotic cell walls......Page 570
16.2 The Extracellular Matrix and Cell–Matrix Interactions......Page 573
Matrix structural proteins......Page 574
Matrix polysaccharides......Page 576
Adhesion proteins......Page 577
Cell–matrix interactions......Page 578
Key Experiment The Characterization of Integrin......Page 579
Adhesion junctions......Page 582
Tight junctions......Page 584
Plasmodesmata......Page 586
Molecular Medicine Gap Junction Diseases......Page 587
Data Analysis Problems......Page 589
Suggested Reading......Page 590
Animations and Videos......Page 591
PART IV: Cell Regulation......Page 592
17.1 Signaling Molecules and Their Receptors......Page 594
Modes of cell-cell signaling......Page 595
Steroid hormones and the nuclear receptor superfamily......Page 596
Signaling by other small molecules......Page 598
Peptide hormones and growth factors......Page 599
17.2 G Proteins and Cyclic AMP......Page 601
G proteins and G protein-coupled receptors......Page 602
Key Experiment G Protein-Coupled Receptors and Odor Detection......Page 603
The cAMP pathway: Second messengers and protein phosphorylation......Page 605
Receptor tyrosine kinases......Page 609
Nonreceptor tyrosine kinases......Page 611
MAP kinase pathways......Page 613
Molecular Medicine Cancer: Signal Transduction and the ras Oncogenes......Page 615
The PI 3-kinase/Akt and mTOR pathways......Page 618
The TGF-B/Smad pathway......Page 623
The Wnt and Notch pathways......Page 624
17.5 Signaling Dynamics and Networks......Page 626
Networks and crosstalk......Page 627
Data Analysis Problems......Page 629
Animations and Videos......Page 630
18.1 The Eukaryotic Cell Cycle......Page 632
Phases of the cell cycle......Page 633
Regulation of the cell cycle by cell growth and extracellular signals......Page 635
Cell cycle checkpoints......Page 637
Protein kinases and cell cycle regulation......Page 639
Key Experiment The Discovery of MPF......Page 640
Key Experiment The Identification of Cyclin......Page 642
Families of cyclins and cyclin-dependent kinases......Page 645
Growth factors and the regulation of G1 Cdk’s......Page 646
S phase and regulation of DNA replication......Page 648
DNA damage checkpoints......Page 650
Stages of mitosis......Page 652
Entry into mitosis......Page 655
The spindle assembly checkpoint and progression to anaphase......Page 658
Cytokinesis......Page 660
Data Analysis Problems......Page 662
Suggested Reading......Page 663
Animations and Videos......Page 664
19.1 Stem Cells and the Maintenance of Adult Tissues......Page 666
Proliferation of differentiated cells......Page 667
Stem cells......Page 669
Medical applications of adult stem cells......Page 674
Embryonic stem cells......Page 676
Key Experiment Culture of Embryonic Stem Cells......Page 678
Somatic cell nuclear transfer......Page 679
Induced pluripotent stem cells......Page 681
Transdifferentiation of somatic cells......Page 683
19.3 Programmed Cell Death......Page 684
The events of apoptosis......Page 685
Key Experiment Identification of Genes Required for Programmed Cell Death......Page 687
Caspases: The executioners of apoptosis......Page 688
Central regulators of apoptosis: The Bcl-2 family......Page 689
Signaling pathways that regulate apoptosis......Page 691
Alternative pathways of programmed cell death......Page 693
Data Analysis Problem......Page 696
Animations and Videos......Page 697
20.1 The Development and Causes of Cancer......Page 698
Types of cancer......Page 699
The development of cancer......Page 700
Properties of cancer cells......Page 701
Causes of cancer......Page 704
20.2 Oncogenes......Page 706
Retroviral oncogenes......Page 707
Proto-oncogenes......Page 708
Key Experiment The Discovery of Proto-Oncogenes......Page 710
Oncogenes in human cancer......Page 711
Functions of oncogene products......Page 714
20.3 Tumor Suppressor Genes......Page 719
Identification of tumor suppressor genes......Page 720
Functions of tumor suppressor gene products......Page 723
Cancer genomics......Page 726
Prevention and early detection......Page 728
Oncogene-targeted drugs......Page 729
Molecular Medicine Imatinib: Cancer Treatment Targeted against the bcr/abl Oncogene......Page 732
Immunotherapy......Page 734
Data Analysis Problem......Page 735
Suggested Reading......Page 736
Animations and Videos......Page 737
Answers to Questions......Page 738
Glossary......Page 766
Illustration Credits......Page 784
Index......Page 786