Re-examining how complexin inhibits neurotransmitter release: SNARE complex insertion or electrostatic hindrance?

Thorsten Trimbuch, Junjie Xu, David Flaherty, Diana R Tomchick, Jose Rizo-Rey, Christian Rosenmund

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Complexins play activating and inhibitory functions in neurotransmitter release. The complexin accessory helix inhibits release and was proposed to insert into SNARE complexes to prevent their full assembly. This model was supported by 'superclamp' and 'poor-clamp' mutations that enhanced or decreased the complexin-I inhibitory activity in cell-cell fusion assays, and by the crystal structure of a superclamp mutant bound to a synaptobrevin-truncated SNARE complex. NMR studies now show that the complexin-I accessory helix does not insert into synaptobrevin-truncated SNARE complexes in solution, and electrophysiological data reveal that superclamp mutants have slightly stimulatory or no effects on neurotransmitter release, whereas a poor-clamp mutant inhibits release. Importantly, increasing or decreasing the negative charge of the complexin-I accessory helix inhibits or stimulates release, respectively. These results suggest a new model whereby the complexin accessory helix inhibits release through electrostatic (and perhaps steric) repulsion enabled by its location between the vesicle and plasma membranes.

Original languageEnglish (US)
Article numbere02391
JournaleLife
Volume2014
Issue number3
DOIs
StatePublished - May 8 2014

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SNARE Proteins
Accessories
Static Electricity
R-SNARE Proteins
Neurotransmitter Agents
Electrostatics
Clamping devices
Cell Fusion
Cell membranes
Cell Membrane
Assays
Mutation
Fusion reactions
Crystal structure
Nuclear magnetic resonance
complexin I

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

Re-examining how complexin inhibits neurotransmitter release : SNARE complex insertion or electrostatic hindrance? / Trimbuch, Thorsten; Xu, Junjie; Flaherty, David; Tomchick, Diana R; Rizo-Rey, Jose; Rosenmund, Christian.

In: eLife, Vol. 2014, No. 3, e02391, 08.05.2014.

Research output: Contribution to journalArticle

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