Recent years have witnessed striking advances in research on axons at a cellular level that substantially impact our current understanding of axonal biology. Newer findings and their ramifications are critically reviewed in the 16 chapters of this volume by authors highly qualified by virtue of their scientific contributions to research areas they know and write about.

Five basic areas (I to V) germane to axonal biology are highlighted, beginning with (I) signaling interactions mediating myelination, and differentiation of axonal membrane domains; (IIa) issues surrounding organization and transport dynamics of neurofilaments in axons, (IIb) mechanisms regulating microtubule organization and dynamics, misregulation of which causes axonal degeneration, and (IIc) the roles actin binding proteins play in regulating organization and functions of the actin filament system in mature and growing axons; (IIIa) myosin motor proteins and cargoes intrinsic to the axon compartment, (IIIb) mitochondrial transport motors, and imperatives governing transport dynamics and directional delivery, (IIIc) mechanisms mediating retrograde signaling associated with NGF's role in trophic-dependent neuronal survival, and (IIId) potential for impaired subcellular targeting of a -synuclein as a mechanism for accumulation of Lewy body inclusions in synucleinopathies; (IVa) occurrence and organization of discrete ribosome-containing domains in axons, (IVb) endogenous mRNAs, classes of proteins translated locally, and RNP trafficking in axons, (IVc) importance of locally synthesized nuclear encoded mitochondrial proteins for maintenance, function and survival of axons, (IVd) occurrence of RNA trafficking from glial cells to axons, and significance glial RNA transcripts may play in expression in axons and axon terminals, (IVe) RNA trafficking and localization of RNA transcripts in axonal growth cones, and signaling pathways that modulate local protein synthesis for directional elongation, and (IVf) genetic and molecular defects underlying spinal muscular atrophy, and roles that SMN gene product plays as a molecular chaperone in mRNA transport and translation; (Va) injury-induced local synthesis of a protein forming a retrograde signaling complex in axons to stimulate regeneration, and (Vb) endogenous and exogenous factors that condition axonal regenerative capacity in PNS and CNS, including injury-induced activation of specific genes governing regeneration.

Emergent complexities revealed in this volume compel a major revision in the traditional conceptual model of the axon's intrinsic makeup and capacities.

1;Contents;5 2;Introduction;7 2.1;References;14 3;Myelination and Regional Domain Differentiation of the Axon;16 3.1;1 Introduction;16 3.2;2 Myelination of Axons;17 3.3;3 Axonal Domains of Myelinated Axons;19 3.4;4 Mechanisms Regulating Axonal Domain Formation and Maintenance;31 3.5;5 Concluding Remarks;35 3.6;References;36 4;Organizational Dynamics, Functions, and Pathobiological Dysfunctions of Neurofilaments;44 4.1;1 Introduction;44 4.2;2 C-Terminal Phosphorylation Regulates NF Axonal Transport;46 4.3;3 NF Transport and Residence Time Along Axons is Regulated by a Combination of Microtubule Motors and C- Terminal NF- H Phosphorylation;48 4.4;4 NF Phosphorylation State and Localization in Neuropathological Conditions: NFs May Contribute to Motor Neuron Disease by Sequestering Motor Proteins and/ or Mitochondria;54 4.5;5 Conclusions and Future Directions;56 4.6;References;57 5;Critical Roles for Microtubules in Axonal Development and Disease;61 5.1;1 Microtubules in the Axon;61 5.2;2 Microtubule-Severing and Hereditary Spastic Paraplegia;67 5.3;3 Tauopathies;70 5.4;4 Other Neurodegenerative Diseases;72 5.5;5 Concluding Remarks;74 5.6;References;74 6;Actin in Axons: Stable Scaffolds and Dynamic Filaments;79 6.1;1 Introduction;79 6.2;2 The Properties of Actin;80 6.3;3 Actin in Axons;81 6.4;4 Actin Functions in Maintaining Axonal Structure;84 6.5;5 Actin Functions in Axonal Transport;86 6.6;6 Actin Functions in Axonal Initiation, Elongation and Guidance;87 6.7;7 Actin Function in Axonal Branching;96 6.8;8 Actin Function in Axonal Retraction;98 6.9;9 Actin Function in Axonal Regeneration;98 6.10;10 Actin Dysfunction in Disease States of Axons;99 6.11;11 Conclusion;99 6.12;References;100 7;Myosin Motor Proteins in the Cell Biology of Axons and Other Neuronal Compartments;105 7.1;1 Introduction;105 7.2;2 Axonal Transport and Neurodegenerative Disease;106 7.3;3 Myosin Transport Motors in neurons;109 7.4;4 Summary;113 7.5;References;114 8;Mitochondrial Transport Dynamics in Axons and Dendrites;120 8.1;1 Introduction;120 8.2;2 How Mitochondria Move in Axons and Dendrites;123 8.3;3 Motors of Mitochondrial Transport;126 8.4;4 Coupling Mitochondria to Motors;130 8.5;5 Regulation of Mitochondrial Motor Activities;133 8.6;6 Targeting of Mitochondria to Specific Sites in Axons and Dendrites;138 8.7;7 Perspective;145 8.8;References;145 9;NGF Uptake and Retrograde Signaling Mechanisms in Sympathetic Neurons in Compartmented Cultures;153 9.1;1 Introduction;153 9.2;2 Conceptual Framework Attendant to Retrograde Signaling;154 9.3;3 Properties of Compartmented Cultures;156 9.4;4 Mechanisms of Retrograde NGF Signaling;158 9.5;5 Evidence for a Retrograde Apoptotic Signal;165 9.6;6 Conclusions;168 9.7;References;169 10;The Paradoxical Cell Biology of a- Synuclein;171 10.1;1 Introduction;171 10.2;2 LB Diseases and the Role of of Synuclein;172 10.3;3 The Neuronal Cell Biology of a- Synuclein;174 10.4;4 Mislocalization of Presynaptic a- Synuclein in LB Dementias;176 10.5;5 Biogenesis and Axonal Transport of wt and Pathologically Altered a- Synuclein;177 10.6;6 Mechanisms of Targeting wt and Pathologic a- Synuclein to Synapses;180 10.7;7 Conclusions and Perspectives;181 10.8;References;182 11;Organized Ribosome-Containing Structural Domains in Axons;185 11.1;1 Introduction;185 11.2;2 Ribosomal RNA (rRNA) in Model Axons;186 11.3;3 Early Random Sightings of Ribosomes in Myelinated Axons;188 11.4;4 Alternative Approaches to Investigate Axonal Ribosomes;188 11.5;5 Periaxoplasmic Ribosomal Plaque (PARP) Domains in Vertebrate Myelinated Axons;190 11.6;6 Transcytosis of Ribosomes from Schwann Cell to the Axon;197 11.7;7 PARPs as Targeted Subdomains for RNA Trafficking in the Axon Compartment;198 11.8;8 Endoaxoplasmic Ribosomal Plaques in Squid Giant Axon;199 11.9;9 Concluding Remarks;201 11.10;References;202 12;Regulation of mRNA Transport and Translation in Axons;204 12.1;1 Both Developing and Adult Neurons Transport mRNAs and Protein Synthesis Machinery into