How synaptotagmin promotes membrane fusion

Science. 2007 May 25;316(5828):1205-8. doi: 10.1126/science.1142614. Epub 2007 May 3.


Synaptic vesicles loaded with neurotransmitters are exocytosed in a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-dependent manner after presynaptic depolarization induces calcium ion (Ca2+) influx. The Ca2+ sensor required for fast fusion is synaptotagmin-1. The activation energy of bilayer-bilayer fusion is very high (approximately 40 k(B)T). We found that, in response to Ca2+ binding, synaptotagmin-1 could promote SNARE-mediated fusion by lowering this activation barrier by inducing high positive curvature in target membranes on C2-domain membrane insertion. Thus, synaptotagmin-1 triggers the fusion of docked vesicles by local Ca2+-dependent buckling of the plasma membrane together with the zippering of SNAREs. This mechanism may be widely used in membrane fusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / physiology*
  • Cell Membrane / physiology*
  • Cell Membrane / ultrastructure
  • Exocytosis / physiology
  • Humans
  • Liposomes
  • Membrane Fusion
  • Models, Biological
  • Rats
  • SNARE Proteins / physiology*
  • Synaptic Vesicles / physiology*
  • Synaptic Vesicles / ultrastructure
  • Synaptotagmin I / physiology*


  • Liposomes
  • SNARE Proteins
  • Synaptotagmin I
  • Calcium