Complexin synchronizes primed vesicle exocytosis and regulates fusion pore dynamics

J Cell Biol. 2014 Mar 31;204(7):1123-40. doi: 10.1083/jcb.201311085.


ComplexinII (CpxII) and SynaptotagminI (SytI) have been implicated in regulating the function of SNARE proteins in exocytosis, but their precise mode of action and potential interplay have remained unknown. In this paper, we show that CpxII increases Ca(2+)-triggered vesicle exocytosis and accelerates its secretory rates, providing two independent, but synergistic, functions to enhance synchronous secretion. Specifically, we demonstrate that the C-terminal domain of CpxII increases the pool of primed vesicles by hindering premature exocytosis at submicromolar Ca(2+) concentrations, whereas the N-terminal domain shortens the secretory delay and accelerates the kinetics of Ca(2+)-triggered exocytosis by increasing the Ca(2+) affinity of synchronous secretion. With its C terminus, CpxII attenuates fluctuations of the early fusion pore and slows its expansion but is functionally antagonized by SytI, enabling rapid transmitter discharge from single vesicles. Thus, our results illustrate how key features of CpxII, SytI, and their interplay transform the constitutively active SNARE-mediated fusion mechanism into a highly synchronized, Ca(2+)-triggered release apparatus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / physiology*
  • Animals
  • Calcium Signaling
  • Cells, Cultured
  • Chromaffin Cells / metabolism
  • Chromaffin Granules / metabolism
  • Exocytosis*
  • Kinetics
  • Membrane Fusion
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / physiology*
  • SNARE Proteins / metabolism
  • Secretory Vesicles / metabolism
  • Synaptotagmins / metabolism
  • Vesicular Transport Proteins


  • Adaptor Proteins, Vesicular Transport
  • Membrane Proteins
  • Nerve Tissue Proteins
  • SNARE Proteins
  • Sytl1 protein, mouse
  • Vesicular Transport Proteins
  • complexin II
  • Synaptotagmins