title: The SNARE protein SNAP-29 interacts with the GTPase Rab3A: Implications for membrane trafficking in myelinating glia.
abstract: During myelin formation, vast amounts of specialized membrane proteins and lipids are trafficked toward the growing sheath in cell surface-directed transport vesicles. Soluble N-ethylmaleimide-sensitive factor (NSF) attachment proteins (SNAPs) are important components of molecular complexes required for membrane fusion. We have analyzed the expression profile and molecular interactions of SNAP-29 in the nervous system. In addition to its known enrichment in neuronal synapses, SNAP-29 is abundant in oligodendrocytes during myelination and in noncompact myelin of the peripheral nervous system. By yeast two-hybrid screen and coimmunoprecipitation, we found that the GTPases Rab3A, Rab24, and septin 4 bind to the N-terminal domain of SNAP-29. The interaction with Rab24 or septin 4 was GTP independent. In contrast, interaction between SNAP-29 and Rab3A was GTP dependent, and colocalization was extensive both in synapses and in myelinating glia. In HEK293 cells, cytoplasmic SNAP-29 pools were redistributed upon coexpression with Rab3A, and surface-directed trafficking of myelin proteolipid protein was enhanced by overexpression of SNAP-29 and Rab3A. Interestingly, the abundance of SNAP-29 in sciatic nerves was increased during remyelination and in a rat model of Charcot-Marie-Tooth disease, two pathological situations with increased myelin membrane biogenesis. We suggest that Rab3A may regulate SNAP-29-mediated membrane fusion during myelination.
authors.affiliation: Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Schardt
authors.forename: Bastian G
authors.initials: BG
authors.lastname: Brinkmann
authors.forename: Miso
authors.initials: M
authors.lastname: Mitkovski
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sereda
authors.forename: Hauke B
authors.initials: HB
authors.lastname: Werner
authors.forename: Klaus-Armin
authors.initials: KA
authors.lastname: Nave
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002607:Charcot-Marie-Tooth Disease / Q000378:metabolism / Q000503:physiopathology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D019204:GTP-Binding Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006160:Guanosine Triphosphate / Q000378:metabolism; D008561:Membrane Fusion / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D050766:Qb-SNARE Proteins / Q000378:metabolism*; D050767:Qc-SNARE Proteins / Q000378:metabolism*; D051381:Rats; D058112:Septins; D013570:Synaptic Membranes / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D020826:rab3A GTP-Binding Protein / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D018991:Myelin Proteolipid Protein; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; C117418:Snap29 protein, rat; D006160:Guanosine Triphosphate; C086224:Rab24 protein, mouse; D019204:GTP-Binding Proteins; C115474:Sept4 protein, mouse; D058112:Septins; D020691:rab GTP-Binding Proteins; D020826:rab3A GTP-Binding Protein