The SNARE protein SNAP-29 interacts with the GTPase Rab3A: Implications for membrane trafficking in myelinating glia

J Neurosci Res. 2009 Nov 15;87(15):3465-79. doi: 10.1002/jnr.22005.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Binding Sites / physiology
  • Cell Differentiation / physiology
  • Cell Line
  • Cell Membrane / metabolism*
  • Cell Membrane / ultrastructure
  • Cells, Cultured
  • Central Nervous System / cytology
  • Central Nervous System / growth & development
  • Central Nervous System / metabolism
  • Charcot-Marie-Tooth Disease / metabolism
  • Charcot-Marie-Tooth Disease / physiopathology
  • Cytoskeletal Proteins / metabolism
  • Disease Models, Animal
  • GTP-Binding Proteins / metabolism
  • Gene Expression Regulation, Developmental / physiology
  • Guanosine Triphosphate / metabolism
  • Membrane Fusion / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Myelin Proteolipid Protein / metabolism
  • Myelin Sheath / metabolism*
  • Myelin Sheath / ultrastructure
  • Nerve Fibers, Myelinated / metabolism*
  • Nerve Fibers, Myelinated / ultrastructure
  • Protein Binding / physiology
  • Protein Structure, Tertiary / physiology
  • Protein Transport / physiology
  • Qb-SNARE Proteins / metabolism*
  • Qc-SNARE Proteins / metabolism*
  • Rats
  • Septins
  • Synaptic Membranes / metabolism
  • Two-Hybrid System Techniques
  • rab GTP-Binding Proteins / metabolism
  • rab3A GTP-Binding Protein / metabolism*


  • Cytoskeletal Proteins
  • Myelin Proteolipid Protein
  • Qb-SNARE Proteins
  • Qc-SNARE Proteins
  • Snap29 protein, rat
  • Guanosine Triphosphate
  • Rab24 protein, mouse
  • GTP-Binding Proteins
  • Sept4 protein, mouse
  • Septins
  • rab GTP-Binding Proteins
  • rab3A GTP-Binding Protein