Transport of the Major Myelin Proteolipid Protein Is Directed by VAMP3 and VAMP7

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