Cell Biology of the Axon (eBook)

Contents 5
Introduction 7
References 14
Myelination and Regional Domain Differentiation of the Axon 16
1 Introduction 16
2 Myelination of Axons 17
3 Axonal Domains of Myelinated Axons 19
4 Mechanisms Regulating Axonal Domain Formation and Maintenance 31
5 Concluding Remarks 35
References 36
Organizational Dynamics, Functions, and Pathobiological Dysfunctions of Neurofilaments 44
1 Introduction 44
2 C-Terminal Phosphorylation Regulates NF Axonal Transport 46
3 NF Transport and Residence Time Along Axons is Regulated by a Combination of Microtubule Motors and C- Terminal NF- H Phosphorylation 48
4 NF Phosphorylation State and Localization in Neuropathological Conditions: NFs May Contribute to Motor Neuron Disease by Sequestering Motor Proteins and/ or Mitochondria 54
5 Conclusions and Future Directions 56
References 57
Critical Roles for Microtubules in Axonal Development and Disease 61
1 Microtubules in the Axon 61
2 Microtubule-Severing and Hereditary Spastic Paraplegia 67
3 Tauopathies 70
4 Other Neurodegenerative Diseases 72
5 Concluding Remarks 74
References 74
Actin in Axons: Stable Scaffolds and Dynamic Filaments 79
1 Introduction 79
2 The Properties of Actin 80
3 Actin in Axons 81
4 Actin Functions in Maintaining Axonal Structure 84
5 Actin Functions in Axonal Transport 86
6 Actin Functions in Axonal Initiation, Elongation and Guidance 87
7 Actin Function in Axonal Branching 96
8 Actin Function in Axonal Retraction 98
9 Actin Function in Axonal Regeneration 98
10 Actin Dysfunction in Disease States of Axons 99
11 Conclusion 99
References 100
Myosin Motor Proteins in the Cell Biology of Axons and Other Neuronal Compartments 105
1 Introduction 105
2 Axonal Transport and Neurodegenerative Disease 106
3 Myosin Transport Motors in neurons 109
4 Summary 113
References 114
Mitochondrial Transport Dynamics in Axons and Dendrites 120
1 Introduction 120
2 How Mitochondria Move in Axons and Dendrites 123
3 Motors of Mitochondrial Transport 126
4 Coupling Mitochondria to Motors 130
5 Regulation of Mitochondrial Motor Activities 133
6 Targeting of Mitochondria to Specific Sites in Axons and Dendrites 138
7 Perspective 145
References 145
NGF Uptake and Retrograde Signaling Mechanisms in Sympathetic Neurons in Compartmented Cultures 153
1 Introduction 153
2 Conceptual Framework Attendant to Retrograde Signaling 154
3 Properties of Compartmented Cultures 156
4 Mechanisms of Retrograde NGF Signaling 158
5 Evidence for a Retrograde Apoptotic Signal 165
6 Conclusions 168
References 169
The Paradoxical Cell Biology of a- Synuclein 171
1 Introduction 171
2 LB Diseases and the Role of of Synuclein 172
3 The Neuronal Cell Biology of a- Synuclein 174
4 Mislocalization of Presynaptic a- Synuclein in LB Dementias 176
5 Biogenesis and Axonal Transport of wt and Pathologically Altered a- Synuclein 177
6 Mechanisms of Targeting wt and Pathologic a- Synuclein to Synapses 180
7 Conclusions and Perspectives 181
References 182
Organized Ribosome-Containing Structural Domains in Axons 185
1 Introduction 185
2 Ribosomal RNA (rRNA) in Model Axons 186
3 Early Random Sightings of Ribosomes in Myelinated Axons 188
4 Alternative Approaches to Investigate Axonal Ribosomes 188
5 Periaxoplasmic Ribosomal Plaque (PARP) Domains in Vertebrate Myelinated Axons 190
6 Transcytosis of Ribosomes from Schwann Cell to the Axon 197
7 PARPs as Targeted Subdomains for RNA Trafficking in the Axon Compartment 198
8 Endoaxoplasmic Ribosomal Plaques in Squid Giant Axon 199
9 Concluding Remarks 201
References 202
Regulation of mRNA Transport and Translation in Axons 204
1 Both Developing and Adult Neurons Transport mRNAs and Protein Synthesis Machinery into their Axons 204
2 A Complex Population of mRNAs Is Transported into Axons 206
3 Axonal mRNAs are Transported as Ribonucleoprotein Particles 217
4 Transport RNPs also Provide Translational Control 218
5 Regulation of Axonal RNA Transport by Extracellular Cues 220
6 Injury as a Stimulus to Shift Axonal mRNA Transport Capacity 223
7 Concluding Remarks 226
References 227
Axonal Protein Synthesis and the Regulation of Local Mitochondrial Function 236
1 Introduction 237
2 Nuclear-Encoded Mitochondrial mRNAs are Present in Invertebrate Axons and Nerve Endings 237
3 Axons of Sympathetic Neurons Contain a Heterogeneous Population of Nuclear- Encoded Mitochondrial mRNAs 239
4 Axonal Protein Synthesis and Mitochondrial Activity 241
5 MicroRNAs in the Axon 244
6 Conclusion 249
References 251
Protein Synthesis in Nerve Terminals and the Glia– Neuron Unit 254
Abbreviations 254
1 Introduction 255
2 Protein Synthesis in Nerve Terminals 256
3 mRNAs in Axons and Nerve Terminals 258
4 Local Glial Synthesis of Neuronal RNA 262
5 Gene Expression in Axons and Nerve Terminals 269
6 Conclusions 271
References 271
Local Translation and mRNA Trafficking in Axon Pathfinding 279
1 Introduction 279
2 Axonal mRNA Localization and Translation: Historical Perspectives 281
3 Identity of Axonal mRNAs 282
4 Molecular Mechanism of Axonal mRNA Transport 283
5 Local Protein Synthesis and Cue-Induced Chemotropic Guidance 287
6 Differential Translation of mRNAs 288
7 Modulation of Chemotropic Response 291
8 Intracellular Signaling Pathways Mediating Local Protein Synthesis 293
9 Conclusion and Perspectives 294
References 294
Spinal Muscular Atrophy and a Model for Survival of Motor Neuron Protein Function in Axonal Ribonucleoprotein Complexes 299
1 Spinal Muscular Atrophy and Survival of Motor Neuron Protein 299
2 SMN Domains and Interacting Proteins 301
3 Localization of SMN and Links to Axonal mRNA Regulation 307
4 A Role for SMN in Stress Granule Formation 312
5 Animal Models of SMA 314
6 Therapeutic Strategies 322
7 Open Questions and Perspectives 324
References 326
Retrograde Injury Signaling in Lesioned Axons 337
1 Introduction 337
2 Rapid Signaling: The Electrophysiological Response 338
3 Negative Injury Signals 339
4 Positive Injury Signals: The Importance of Importins 340
5 Other Modes of Linkage to the Retrograde Injury- Signaling Complex 342
6 Neurotrophins as Positive Injury Signals 343
7 The Cell Body Response to Axonal Injury 344
8 Summary 345
References 345
Axon Regeneration in the Peripheral and Central Nervous Systems 349
1 Introduction 349
2 Axon Regeneration in the Peripheral Nervous System 350
3 Axon Regeneration in the Central Nervous System 351
4 Conclusion 357
References 357
Index 362