Binding of the complexin N terminus to the SNARE complex potentiates synaptic-vesicle fusogenicity

Nat Struct Mol Biol. 2010 May;17(5):568-75. doi: 10.1038/nsmb.1791. Epub 2010 Apr 18.


Complexins facilitate and inhibit neurotransmitter release through distinct domains, and their function was proposed to be coupled to the Ca(2+) sensor synaptotagmin-1 (Syt1). However, the mechanisms underlying complexin function remain unclear. We now uncover an interaction between the complexin N terminus and the SNARE complex C terminus, and we show that disrupting this interaction abolishes the facilitatory function of complexins in mouse neurons. Analyses of hypertonically induced exocytosis show that complexins enhance synaptic-vesicle fusogenicity. Genetic experiments crossing complexin- and Syt1-null mice indicate a functional interaction between these proteins but also show that complexins can promote Ca(2+)-triggered release in the absence of Syt1. We propose that the complexin N terminus stabilizes the SNARE complex C terminus and/or helps release the inhibitory function of complexins, thereby activating the fusion machinery in a manner that may cooperate with Syt1 but does not require Syt1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / chemistry*
  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism*
  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism
  • Cells, Cultured
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Protein Conformation
  • Rats
  • SNARE Proteins / chemistry
  • SNARE Proteins / metabolism*
  • Synaptic Vesicles / metabolism*
  • Synaptotagmin I / genetics
  • Synaptotagmin I / metabolism


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