Synaptic Vesicle Fusion Complex Contains unc-18 Homologue Bound to Syntaxin

Nature. 1993 Nov 25;366(6453):347-51. doi: 10.1038/366347a0.

Abstract

Three synaptic proteins, syntaxin, SNAP-25 and synaptobrevin, were recently identified as targets of clostridial neurotoxins that irreversibly inhibit synaptic vesicle fusion. Experiments searching for membrane receptors for N-ethylmaleimide-sensitive fusion protein (NSF), which has an important role in membrane fusion, revealed an ATP-dependent interaction of the same three synaptic proteins with NSF and its soluble attachment proteins. Thus, two independent approaches identify syntaxin, synaptobrevin and SNAP-25 as components of the synaptic vesicle fusion machinery, but their mode of action is unclear. We have now discovered a brain protein of relative molecular mass 67,000 (67K) which binds stably to syntaxin. Amino-acid sequencing and complementary DNA cloning revealed that the 67K protein is encoded by the mammalian homologue of the Caenorhabditis elegans gene unc-18. In C. elegans, unc-18 belongs to a group of genes defined by mutations with a paralytic phenotype and accumulations of acetylcholine, suggesting a defect in neurotransmitter release. The binding of the mammalian homologue of unc-18 (Munc-18) to syntaxin requires the N terminus of syntaxin whereas that of SNAP-25 involves a more C-terminal sequence. Our data suggest that Munc-18 is a previously unidentified essential component of the synaptic vesicle fusion protein complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Surface / metabolism
  • Base Sequence
  • Brain Chemistry
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins*
  • Carrier Proteins*
  • Cattle
  • Helminth Proteins / chemistry
  • Membrane Fusion / physiology*
  • Molecular Sequence Data
  • Munc18 Proteins
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Phosphoproteins*
  • Protein Binding
  • Rats
  • Recombinant Fusion Proteins
  • Sequence Homology, Amino Acid
  • Synaptic Vesicles / physiology*
  • Syntaxin 1
  • Vesicular Transport Proteins*

Substances

  • Antigens, Surface
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Helminth Proteins
  • Munc18 Proteins
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • Syntaxin 1
  • Unc-18 protein, C elegans
  • Vesicular Transport Proteins

Associated data

  • GENBANK/L26087
  • GENBANK/L26088