Transport of the major myelin proteolipid protein is directed by VAMP3 and VAMP7

J Neurosci. 2011 Apr 13;31(15):5659-72. doi: 10.1523/JNEUROSCI.6638-10.2011.


CNS myelination by oligodendrocytes requires directed transport of myelin membrane components and a timely and spatially controlled membrane expansion. In this study, we show the functional involvement of the R-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (R-SNARE) proteins VAMP3/cellubrevin and VAMP7/TI-VAMP in myelin membrane trafficking. VAMP3 and VAMP7 colocalize with the major myelin proteolipid protein (PLP) in recycling endosomes and late endosomes/lysosomes, respectively. Interference with VAMP3 or VAMP7 function using small interfering RNA-mediated silencing and exogenous expression of dominant-negative proteins diminished transport of PLP to the oligodendroglial cell surface. In addition, the association of PLP with myelin-like membranes produced by oligodendrocytes cocultured with cortical neurons was reduced. We furthermore identified Syntaxin-4 and Syntaxin-3 as prime acceptor Q-SNAREs of VAMP3 and VAMP7, respectively. Analysis of VAMP3-deficient mice revealed no myelination defects. Interestingly, AP-3δ-deficient mocha mice, which suffer from impaired secretion of lysosome-related organelles and missorting of VAMP7, exhibit a mild dysmyelination characterized by reduced levels of select myelin proteins, including PLP. We conclude that PLP reaches the cell surface via at least two trafficking pathways with distinct regulations: (1) VAMP3 mediates fusion of recycling endosome-derived vesicles with the oligodendroglial plasma membrane in the course of the secretory pathway; (2) VAMP7 controls exocytosis of PLP from late endosomal/lysosomal organelles as part of a transcytosis pathway. Our in vivo data suggest that exocytosis of lysosome-related organelles controlled by VAMP7 contributes to myelin biogenesis by delivering cargo to the myelin membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport, Active / physiology
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Electrophoresis, Polyacrylamide Gel
  • Endosomes / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Exocytosis / physiology
  • Female
  • Genetic Vectors
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Lysosomes / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Immunoelectron
  • Myelin Proteolipid Protein / metabolism*
  • Myelin Sheath / metabolism
  • R-SNARE Proteins / metabolism*
  • RNA Interference
  • Transfection
  • Vesicle-Associated Membrane Protein 3 / metabolism*


  • Myelin Proteolipid Protein
  • R-SNARE Proteins
  • Sybl1 protein, mouse
  • Vesicle-Associated Membrane Protein 3