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Conformational switch of syntaxin-1 controls synaptic vesicle fusion.

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


  • Gerber SH
  • Rah JC
  • Min SW
  • Liu X
  • de Wit H
  • Dulubova I
  • Meyer AC
  • Rizo J
  • Arancillo M
  • Hammer RE
  • Verhage M
  • Rosenmund C
  • S├╝dhof TC


Science (New York, N.Y.)

Publication Data

September 12, 2008

Associated Grants

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

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