Distinct domains of complexin I differentially regulate neurotransmitter release

Nat Struct Mol Biol. 2007 Oct;14(10):949-58. doi: 10.1038/nsmb1292. Epub 2007 Sep 9.


Complexins constitute a family of four synaptic high-affinity SNARE complex-binding proteins. They positively regulate a late, post-priming step in Ca2+-triggered synchronous neurotransmitter release, but the underlying molecular mechanisms are unclear. We show here that SNARE complex binding of complexin I (CplxI) via its central alpha-helix is necessary but, unexpectedly, not sufficient for its key function in promoting neurotransmitter release. An accessory alpha-helix on the N-terminal side of the SNARE complex-binding region has an inhibitory effect on fast synaptic exocytosis, whereas sequences N-terminally adjacent to this helix facilitate Ca2+-triggered release even in the absence of the Ca2+ sensor synaptotagmin-1. Our results indicate that distinct functional domains of CplxI differentially regulate synaptic exocytosis and that, through the interplay between these domains, CplxI carries out a crucial role in fine-tuning Ca2+-triggered fast neurotransmitter release.

Publication types

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

MeSH terms

  • Adaptor Proteins, Vesicular Transport
  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism
  • Cells, Cultured
  • Exocytosis / physiology
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology
  • Neurons / physiology
  • Neurotransmitter Agents / metabolism*
  • Patch-Clamp Techniques
  • Presynaptic Terminals / metabolism
  • Protein Binding
  • Protein Structure, Secondary*
  • Protein Structure, Tertiary
  • Rats
  • SNARE Proteins / metabolism*
  • Sequence Alignment
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / metabolism
  • Synaptotagmin I / metabolism


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