Diffusional spread and confinement of newly exocytosed synaptic vesicle proteins

Nat Commun. 2015 Sep 24:6:8392. doi: 10.1038/ncomms9392.


Neurotransmission relies on the calcium-triggered exocytic fusion of non-peptide neurotransmitter-containing small synaptic vesicles (SVs) with the presynaptic membrane at active zones (AZs) followed by compensatory endocytic retrieval of SV membranes. Here, we study the diffusional fate of newly exocytosed SV proteins in hippocampal neurons by high-resolution time-lapse imaging. Newly exocytosed SV proteins rapidly disperse within the first seconds post fusion until confined within the presynaptic bouton. Rapid diffusional spread and confinement is followed by slow reclustering of SV proteins at the periactive endocytic zone. Confinement within the presynaptic bouton is mediated in part by SV protein association with the clathrin-based endocytic machinery to limit diffusional spread of newly exocytosed SV proteins. These data suggest that diffusion, and axonal escape of newly exocytosed vesicle proteins, are counteracted by the clathrin-based endocytic machinery together with a presynaptic diffusion barrier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Diffusion
  • Endocytosis*
  • Exocytosis*
  • Hippocampus / cytology
  • Immunohistochemistry
  • Mice
  • Microscopy, Fluorescence
  • Models, Biological
  • Monomeric Clathrin Assembly Proteins / genetics*
  • Monomeric Clathrin Assembly Proteins / metabolism
  • Neurons / metabolism*
  • Presynaptic Terminals / metabolism*
  • Synaptic Transmission*
  • Synaptic Vesicles / metabolism*
  • Synaptophysin / metabolism
  • Synaptotagmin I / metabolism
  • Time-Lapse Imaging
  • Vesicle-Associated Membrane Protein 2 / metabolism


  • Monomeric Clathrin Assembly Proteins
  • PICALM protein, mouse
  • Synaptophysin
  • Synaptotagmin I
  • Syp protein, mouse
  • Syt1 protein, mouse
  • Vesicle-Associated Membrane Protein 2
  • clathrin assembly protein AP180
  • vesicle-associated membrane protein 2, mouse
  • Calcium