Format

Send to

Choose Destination
Elife. 2014 May 8;3:e02391. doi: 10.7554/eLife.02391.

Re-examining how complexin inhibits neurotransmitter release.

Author information

1
NeuroCure Cluster of Excellence, Neuroscience Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
2
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States.
3
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States jose@arnie.swmed.edu.
4
NeuroCure Cluster of Excellence, Neuroscience Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany christian.rosenmund@charite.de.

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.DOI: http://dx.doi.org/10.7554/eLife.02391.001.

KEYWORDS:

membrane fusion; protein interactions; synaptic vesicle exocytosis

PMID:
24842998
PMCID:
PMC4040926
DOI:
10.7554/eLife.02391
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center