Complexin arrests a pool of docked vesicles for fast Ca2+-dependent release

EMBO J. 2012 Aug 1;31(15):3270-81. doi: 10.1038/emboj.2012.164. Epub 2012 Jun 15.


Regulated exocytosis requires that the assembly of the basic membrane fusion machinery is temporarily arrested. Synchronized membrane fusion is then caused by a specific trigger--a local rise of the Ca(2+) concentration. Using reconstituted giant unilamellar vesicles (GUVs), we have analysed the role of complexin and membrane-anchored synaptotagmin 1 in arresting and synchronizing fusion by lipid-mixing and cryo-electron microscopy. We find that they mediate the formation and consumption of docked small unilamellar vesicles (SUVs) via the following sequence of events: Synaptotagmin 1 mediates v-SNARE-SUV docking to t-SNARE-GUVs in a Ca(2+)-independent manner. Complexin blocks vesicle consumption, causing accumulation of docked vesicles. Together with synaptotagmin 1, complexin synchronizes and stimulates rapid fusion of accumulated docked vesicles in response to physiological Ca(2+) concentrations. Thus, the reconstituted assay resolves both the stimulatory and inhibitory function of complexin and mimics key aspects of synaptic vesicle fusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / chemistry
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Adaptor Proteins, Vesicular Transport / physiology*
  • Biological Transport / drug effects
  • Biological Transport / physiology
  • Calcium / pharmacology*
  • Exocytosis / drug effects
  • Exocytosis / physiology
  • Humans
  • In Vitro Techniques
  • Membrane Fusion / drug effects
  • Models, Biological
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Protein Binding / drug effects
  • Synaptic Transmission / drug effects
  • Synaptic Vesicles / drug effects*
  • Synaptic Vesicles / metabolism*
  • Synaptotagmin I / chemistry
  • Synaptotagmin I / metabolism
  • Synaptotagmin I / physiology
  • Time Factors
  • Unilamellar Liposomes / metabolism


  • Adaptor Proteins, Vesicular Transport
  • Nerve Tissue Proteins
  • Synaptotagmin I
  • Unilamellar Liposomes
  • complexin I
  • Calcium