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Science. 2008 Sep 12;321(5895):1507-10. doi: 10.1126/science.1163174. Epub 2008 Aug 14.

Conformational switch of syntaxin-1 controls synaptic vesicle fusion.

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  • 1Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.

Abstract

During synaptic vesicle fusion, the soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) protein syntaxin-1 exhibits two conformations that both bind to Munc18-1: a "closed" conformation outside the SNARE complex and an "open" conformation in the SNARE complex. Although SNARE complexes containing open syntaxin-1 and Munc18-1 are essential for exocytosis, the function of closed syntaxin-1 is unknown. We generated knockin/knockout mice that expressed only open syntaxin-1B. Syntaxin-1B(Open) mice were viable but succumbed to generalized seizures at 2 to 3 months of age. Binding of Munc18-1 to syntaxin-1 was impaired in syntaxin-1B(Open) synapses, and the size of the readily releasable vesicle pool was decreased; however, the rate of synaptic vesicle fusion was dramatically enhanced. Thus, the closed conformation of syntaxin-1 gates the initiation of the synaptic vesicle fusion reaction, which is then mediated by SNARE-complex/Munc18-1 assemblies.

PMID:
18703708
[PubMed - indexed for MEDLINE]
PMCID:
PMC3235364
Free PMC Article

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