Synaptobrevin is essential for fast synaptic-vesicle endocytosis

Nat Cell Biol. 2004 Nov;6(11):1102-8. doi: 10.1038/ncb1185. Epub 2004 Oct 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Endocytosis / physiology*
  • Horseradish Peroxidase / metabolism
  • In Vitro Techniques
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Microscopy, Electron
  • Pyridinium Compounds / metabolism
  • Quaternary Ammonium Compounds / metabolism
  • R-SNARE Proteins
  • Synaptic Vesicles / metabolism
  • Synaptic Vesicles / physiology*


  • FM1 43
  • Membrane Proteins
  • Pyridinium Compounds
  • Quaternary Ammonium Compounds
  • R-SNARE Proteins
  • Horseradish Peroxidase