Protein Trafficking in Neurons

Title page......Page 5
Copyright page......Page 6
Table of contents......Page 9
Contributors......Page 15
Acknowledgments......Page 17
SECTION I: PROTEIN MOVEMENT......Page 19
CHAPTER 1: Molecular Mobility in Cells Examined with Optical Methods......Page 21
I. BROWNIAN MOTION AND THE FUNDAMENTALS OF DIFFUSION......Page 22
II. A VIEW OF CYTOPLASM AND MEMBRANE FROM THE SINGLE MOLECULE PERSPECTIVE......Page 24
III. DIFFUSION AND MOBILITY OF PROTEINS IN CELLS STUDIED WITH BIOPHYSICAL TECHNIQUES......Page 29
IV. CONCLUSIONS AND FUTURE DIRECTIONS......Page 42
I. INTRODUCTION......Page 47
II. KINESIN......Page 48
III. CYTOPLASMIC DYNEIN......Page 49
IV. DYNACTIN......Page 50
VI. TRANSPORT REGULATION AND CONTROL......Page 51
VIII. PROTEIN DEGRADATION......Page 52
IX. mRNA LOCALIZATION......Page 53
XI. AXON SIGNALING STRATEGY......Page 54
XIII. SURVIVAL SIGNALING......Page 55
XVI. NEURODEGENERATIVE DISEASE......Page 56
References......Page 57
CHAPTER 3: Role of APC Complexes and the Microtubule Cytoskeleton in Neuronal Morphogenesis......Page 63
II. ROLE OF MICROTUBULES IN NEURONAL POLARIZATION......Page 64
III. TARGETING OF APC TO TIPS OF NEURITES......Page 66
IV. ROLE OF APC IN MICROTUBULE DYNAMICS AT TIPS OF NEURITES......Page 70
V. SUMMARY......Page 73
References......Page 74
SECTION II: SYNAPTIC DEVELOPMENT......Page 79
CHAPTER 4: Assembly of Synapses in the Vertebrate Central Nervous System......Page 81
II. CELL BIOLOGY OF CNS SYNAPSES......Page 82
III. MOLECULAR MECHANISMS OF SYNAPSE FORMATION......Page 84
IV. SYNAPTIC SPECIFICITY AND MOLECULAR DIVERSITY OF CELL SURFACE RECEPTORS......Page 88
References......Page 89
CHAPTER 5: Presynaptic Terminal Differentiation......Page 93
II. PROTEIN COMPONENTS OF PRESYNAPTIC TERMINI......Page 94
III. SNAREs......Page 95
IV. FUTURE PERSPECTIVES......Page 106
References......Page 107
SECTION III: EXO-/ENDOCYTOSIS......Page 113
I. INTRODUCTION......Page 115
II. CONCLUSIONS......Page 133
References......Page 134
I. ENDOCYTOSIS IN NEURONS......Page 143
II. THE CLATHRIN-DEPENDENT ENDOCYTIC MACHINERY......Page 144
III. MECHANISMS OF PRESYNAPTIC VESICLE CYCLING......Page 147
IV. ENDOCYTOSIS OF POSTSYNAPTIC NEUROTRANSMITTER RECEPTORS......Page 151
V. CONCLUSIONS......Page 153
References......Page 154
SECTION IV: RECEPTOR TRAFFICKING......Page 159
CHAPTER 8: Postsynaptic Machinery for Receptor Trafficking......Page 161
I. POSTSYNAPTIC MICROANATOMY: DENDRITES AND SPINES......Page 162
II. TRAFFICKING OF NEW RECEPTORS: DENDRITIC SECRETORY ORGANELLES......Page 167
III. ENDOCYTOSIS AND THE ENDOCYTIC ZONE......Page 173
IV. ENDOSOMES AND RECEPTOR RECYCLING......Page 180
V. THE EXTRASYNAPTIC PLASMA MEMBRANE AND LATERAL MOVEMENT OF RECEPTORS......Page 183
VI. PERSPECTIVES......Page 185
References......Page 186
I. INTRODUCTION......Page 193
II. REGULATED RECEPTOR ASSEMBLY AND EXIT FROM THE ER......Page 196
III. DENDRITIC LOCALIZATION AND MEMBRANE INSERTION......Page 198
IV. RETENTION AND CONSTITUTIVE CYCLING AT THE SYNAPSE......Page 200
V. REGULATED SYNAPTIC TARGETING......Page 205
References......Page 211
I. INTRODUCTION......Page 221
II. ASSEMBLY OF NMDA-Rs......Page 222
III. EXITING THE ENDOPLASMIC RETICULUM—THE ROLE OF NR1 SUBUNIT......Page 224
IV. RELEASING THE RETENTION FROM THE ER—THE ROLE OF NR2 SUBUNITS......Page 225
VI. TARGETING NMDA RECEPTORS TO THE SYNAPSE......Page 226
VII. ACTIVITY-DEPENDENT CHANGES IN NMDA RECEPTOR SUBUNIT LOCALIZATION......Page 230
VIII. TRAFFICKING REGULATION BY PHOSPHORYLATION......Page 232
IX. INTERNALIZATION OF NMDA RECEPTORS......Page 233
References......Page 234
SECTION V: TRAFFICKING OF ION CHANNELS AND TRANSPORTERS......Page 241
I. INTRODUCTION......Page 243
II. PLASMA MEMBRANE NEUROTRANSMITTER TRANSPORTERS......Page 244
III. VESICULAR MONOAMINE AND ACETYLCHOLINE TRANSPORTERS......Page 246
IV. VESICULAR GLUTAMATE TRANSPORTERS......Page 251
V. CONCLUSIONS......Page 254
References......Page 255
CHAPTER 12: Determinants of Voltage-Gated Potassium Channel Distribution in Neurons......Page 261
I. INTRODUCTION......Page 262
II. MOLECULAR PROPERTIES OF Kv CHANNELS......Page 263
III. DETERMINANTS OF INTRACELLULAR TRAFFICKING OF Kv CHANNELS......Page 267
IV. DETERMINANTS OF POLARIZED DISTRIBUTION OF Kv CHANNELS......Page 275
V. PATHOLOGICAL ALTERATIONS IN Kv CHANNEL TRAFFICKING AND DISTRIBUTION......Page 278
VI. FUTURE DIRECTIONS......Page 280
References......Page 281
SECTION VI: TRAFFICKING IN OTHER CELL TYPES......Page 287
CHAPTER 13: Protein Trafficking in the Exocytic Pathway of Polarized Epithelial Cells......Page 289
II. POLARIZED TRAFFICKING......Page 290
III. CARGO SORTING MECHANISMS IN THE BIOSYNTHETIC ROUTES......Page 295
IV. ROLE OF THE CYTOSKELETON IN POLARIZED TRAFFICKING IN EPITHELIAL CELLS......Page 302
V. TETHERING, DOCKING, AND FUSION OF TRANSPORT INTERMEDIATES......Page 306
References......Page 310
I. INTRODUCTION......Page 323
II. BIOGENESIS OF DCVs IN THE GOLGI AND THEIR MATURATION......Page 324
III. CYTOPLASMIC TRANSPORT OF DCVs IS MEDIATED BY KINESIN AND MYOSIN......Page 325
IV. DCVs ARE TETHERED AT THE PLASMA MEMBRANE PRIOR TO FUSION......Page 326
V. WHAT MEDIATES DCV TETHERING TO THE PLASMA MEMBRANE?......Page 327
VI. DOCKED DCVs REQUIRE ATP-DEPENDENT PRIMING PRIOR TO FUSION......Page 329
VII. PI(4,5)P2 SYNTHESIS IS AN ESSENTIAL COMPONENT OF DCV PRIMING......Page 330
VIII. WHY IS PI(4,5)P2 REQUIRED FOR DCV EXOCYTOSIS?......Page 331
IX. SNARES ARE AT THE CORE OF DCV FUSION......Page 332
X. SYNAPTOTAGMINS SENSE CALCIUM AND TRIGGER SNARE-DEPENDENT DCV FUSION......Page 334
XI. DCV FUSION PORES DILATE OR CLOSE......Page 335
XII. DYNAMIN MEDIATES PRECOCIOUS DCV FUSION PORE CLOSURE......Page 337
XIII. CAVICAPTURE ALLOWS SELECTIVE RELEASE OF DCV CONSTITUENTS......Page 338
References......Page 339
CHAPTER 15: Exocytic Release of Glutamate from Astrocytes: Comparison to Neurons......Page 347
II. EXCITABILITY AND INTERCELLULAR COMMUNICATION......Page 348
III. Ca-DEPENDENT EXOCYTIC RELEASE OF GLUTAMATE......Page 354
IV. VESICULAR TRAFFICKING......Page 370
V. INPUT AND RELEASE SITES ON ASTROCYTES......Page 371
VI. CONCLUDING REMARKS......Page 375
References......Page 376
SECTION VII: PROTEIN TRAFFICKING AND NEURONAL DISEASE......Page 385
I. GENERAL CONSIDERATIONS......Page 387
II. EVIDENCE THAT htt IS A TRAFFICKING PROTEIN......Page 389
III. INHIBITION OF TRAFFICKING: A PRIMARY DEFECT OR A CONSEQUENCE OF AGGREGATION?......Page 395
IV. TRAFFICKING VERSUS NUCLEAR TOXICITY......Page 397
V. COMMON TIES BETWEEN HD AND OTHER NEURODEGENERATIVE DISORDERS......Page 398
VI. CYTOSKELETAL AND VESICULAR DYSFUNCTION......Page 399
VII. MOTOR PROTEINS......Page 400
References......Page 402
CHAPTER 17: Neuronal Protein Trafficking in Alzheimer’s Disease and Niemann-Pick Type C Disease......Page 409
II. ALZHEIMER’S DISEASE......Page 410
III. NIEMANN-PICK DISEASE......Page 415
IV. NPC AND AD: COMMON PATHOLOGIES......Page 420
References......Page 423
I. INTRODUCTION......Page 431
II. A BRIEF HISTORY OF PRION DISEASES......Page 432
III. THE CONCEPT OF A PrP-DERIVED PROTEOME......Page 434
IV. PrP BIOSYNTHESIS......Page 436
V. INTRACELLULAR TRAFFICKING OF PrP......Page 441
VI. PrP DEGRADATION......Page 443
VII. THE IMPACT OF PrPSc ON PrPC BIOSYNTHESIS, TRAFFICKING, AND DEGRADATION......Page 445
References......Page 447
Index......Page 455