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

By Anke Feldmann, Jesa Amphornrat, Madeleine Schönherr, Christine Winterstein, Wiebke Möbius, Torben Ruhwedel, Lydia Danglot, Klaus-Armin Nave, Thierry Galli, Dieter Bruns, Jacqueline Trotter and Eva-Maria Krämer-Albers

Abstract

International audienceCNS 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

Topics: MESH : Animals, MESH : Biological Transport, Active, MESH : Image Processing, Computer-Assisted, MESH : Immunohistochemistry, MESH : Lysosomes, MESH : Male, MESH : Mice, MESH : Mice, Inbred C57BL, MESH : Microscopy, Immunoelectron, MESH : Myelin Proteolipid Protein, MESH : Myelin Sheath, MESH : R-SNARE Proteins, MESH : Cell Membrane, MESH : RNA Interference, MESH : Transfection, MESH : Vesicle-Associated Membrane Protein 3, MESH : Cells, Cultured, MESH : Electrophoresis, Polyacrylamide Gel, MESH : Endosomes, MESH : Enzyme-Linked Immunosorbent Assay, MESH : Exocytosis, MESH : Female, MESH : Genetic Vectors, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Publisher: Society for Neuroscience
Year: 2011
DOI identifier: 10.1523/JNEUROSCI.6638-10.2011
OAI identifier: oai:HAL:hal-00606080v1
Provided by: Hal-Diderot
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