Synaptic vesicle fusion complex contains unc-18 homologue bound to syntaxin

Yutaka Hata, Clive A. Slaughter, Thomas C. Südhof

Research output: Contribution to journalArticle

538 Citations (Scopus)

Abstract

THREE synaptic proteins, syntaxin, SNAP-25 and synaptobrevin, were recently identified as targets of clostridial neurotoxins that irreversibly inhibit synaptic vesicle fusion1-4. Experiments searching for membrane receptors forN-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 5. Thus, two independent approaches identify syntaxin, synaptobrevin and SNAP-25 as components of the synaptic vesicle fusion machinery, but their mode of action is unclear6. 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 release7,8. 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.

Original languageEnglish (US)
Pages (from-to)347-351
Number of pages5
JournalNature
Volume366
Issue number6453
DOIs
StatePublished - Jan 1 1993
Externally publishedYes

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Qa-SNARE Proteins
Synaptic Vesicles
R-SNARE Proteins
Caenorhabditis elegans
Proteins
Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins
Synaptosomal-Associated Protein 25
Tetanus Toxin
Membrane Fusion
Ethylmaleimide
Protein Sequence Analysis
Genes
Acetylcholine
Neurotransmitter Agents
Organism Cloning
Complementary DNA
Adenosine Triphosphate
Phenotype
Mutation
Membranes

ASJC Scopus subject areas

  • General

Cite this

Synaptic vesicle fusion complex contains unc-18 homologue bound to syntaxin. / Hata, Yutaka; Slaughter, Clive A.; Südhof, Thomas C.

In: Nature, Vol. 366, No. 6453, 01.01.1993, p. 347-351.

Research output: Contribution to journalArticle

Hata, Yutaka ; Slaughter, Clive A. ; Südhof, Thomas C. / Synaptic vesicle fusion complex contains unc-18 homologue bound to syntaxin. In: Nature. 1993 ; Vol. 366, No. 6453. pp. 347-351.
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