Synaptobrevin is essential for fast synaptic-vesicle endocytosis.
Synaptobrevin-2 (VAMP-2), the major SNARE protein of synaptic vesicles, is required for fast calcium-triggered synaptic-vesicle exocytosis. Here we show that synaptobrevin-2 is also essential for fast synaptic-vesicle endocytosis. We demonstrate that after depletion of the readily releasable vesicle pool, replenishment of the pool is delayed by knockout of synaptobrevin. This delay was not from a loss of vesicles, because the total number of pre-synaptic vesicles, docked vesicles and actively recycling vesicles was unaffected. However, altered shape and size of the vesicles in synaptobrevin-deficient synapses suggests a defect in endocytosis. Consistent with such a defect, the stimulus-dependent endocytosis of horseradish peroxidase and fluorescent FM1-43 were delayed, indicating that fast vesicle endocytosis may normally be nucleated by a SNARE-dependent coat. Thus, synaptobrevin is essential for two fast synapse-specific membrane trafficking reactions: fast exocytosis for neurotransmitter release and fast endocytosis that mediates rapid reuse of synaptic vesicles.
Center for Basic Neuroscience, Howard Hughes Medical Institute, USA.
Ferenc
F
Deák
Susanne
S
Schoch
Xinran
X
Liu
Thomas C
TC
Südhof
Ege T
ET
Kavalali
D000818:Animals; D004705:Endocytosis / Q000502:physiology*; D006735:Horseradish Peroxidase / Q000378:metabolism; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D011726:Pyridinium Compounds / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D050683:R-SNARE Proteins; D013572:Synaptic Vesicles / Q000378:metabolism / Q000502:physiology*
C073804:FM1 43; D008565:Membrane Proteins; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D050683:R-SNARE Proteins; D006735:Horseradish Peroxidase