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Conformational switch of syntaxin-1 controls synaptic vesicle fusion.

Science (New York, N.Y.) | Sep 12, 2008

http://www.ncbi.nlm.nih.gov/pubmed/18703708

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.

Pubmed ID: 18703708 RIS Download

Mesh terms: Animals | Calcium | Epilepsy | Excitatory Postsynaptic Potentials | Membrane Fusion | Mice | Mice, Knockout | Munc18 Proteins | Mutation | Protein Conformation | Protein Structure, Tertiary | SNARE Proteins | Sucrose | Synapses | Synaptic Vesicles | Syntaxin 1

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Associated grants

  • Agency: NINDS NIH HHS, Id: NS051262
  • Agency: NINDS NIH HHS, Id: NS37200
  • Agency: Howard Hughes Medical Institute, Id:

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