Vesicular proteins exocytosed and subsequently retrieved by compensatory endocytosis are nonidentical

Nat Neurosci. 2006 Aug;9(8):1019-27. doi: 10.1038/nn1739. Epub 2006 Jul 16.


Upon exocytosis, synaptic vesicle proteins are released into the plasma membrane and have to be retrieved by compensatory endocytosis. When green fluorescent protein-labeled versions of the vesicle proteins synaptobrevin-2 and synaptotagmin-1 are overexpressed in rat hippocampal neurons, up to 30% are found on axonal membranes under resting conditions. To test whether and to what extent these plasma membrane-stranded proteins participate in exo-endocytic cycling, a new proteolytic approach was used to visualize the fate of newly exocytosed proteins separately from that of the plasma membrane-stranded ones. We found that both pools were mixed and that endocytosed vesicles were largely composed of previously stranded molecules. The degree of nonidentity of vesicular proteins exo- and endocytosed depended on stimulus duration. By using an antibody to the external domain of synaptotagmin-1, we estimated that under physiological conditions a few percent of vesicular proteins were located near the active zone, from where they were preferentially recycled upon stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Endocytosis / physiology*
  • Exocytosis / physiology*
  • Hippocampus / cytology
  • Membrane Fusion
  • Neurons / cytology
  • Neurons / metabolism
  • Rats
  • Rats, Wistar
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Synaptic Vesicles* / chemistry
  • Synaptic Vesicles* / metabolism
  • Synaptotagmin I / genetics
  • Synaptotagmin I / metabolism*
  • Vesicle-Associated Membrane Protein 2 / genetics
  • Vesicle-Associated Membrane Protein 2 / metabolism*


  • Recombinant Fusion Proteins
  • Synaptotagmin I
  • Syt1 protein, rat
  • Vamp2 protein, rat
  • Vesicle-Associated Membrane Protein 2