Synaptic vesicle membrane fusion complex

Action of clostridial neurotoxins on assembly

Tetsuya Hayashi, Harvey McMahon, Shinji Yamasaki, Thomas Binz, Yutaka Hata, Thomas C. Südhof, Heiner Niemann

Research output: Contribution to journalArticle

625 Citations (Scopus)

Abstract

Clostridial neurotoxins inhibit neurotransmitter release by selective and specific intracellular proteolysis of synaptobrevin/VAMP, synaptosomal-associated protein of 25 kDa (SNAP-25) or syntaxin. Here we show that in binary reactions synaptobrevin binds weakly to both SNAP-25 and syntaxin, and SNAP-25 binds to syntaxin. In the presence of all three components, a dramatic increase in the interaction strengths occurs and a stable sodium dodecyl sulfate-resistant complex forms. Mapping of the interacting sequences reveals that complex formation correlates with the presence of predicted α-helical structures, suggesting that membrane fusion involves intermolecular interactions via coiled-coil structures. Most toxins only attack the free, and not the complexed, proteins, and proteolysis of the proteins by different clostridial neurotoxins has distinct inhibitory effects on the formation of synaptobrevin-syntaxin-SNAP-25 complexes. Our data suggest that synaptobrevin, syntaxin and SNAP-25 associate into a unique stable complex that functions in synaptic vesicle exocytosis.

Original languageEnglish
Pages (from-to)5051-5061
Number of pages11
JournalEMBO Journal
Volume13
Issue number21
Publication statusPublished - Nov 23 1994
Externally publishedYes

Fingerprint

Synaptosomal-Associated Protein 25
Qa-SNARE Proteins
Tetanus Toxin
Synaptic Membranes
Membrane Fusion
R-SNARE Proteins
Synaptic Vesicles
Fusion reactions
Membranes
Proteolysis
Exocytosis
Sodium Dodecyl Sulfate
Neurotransmitter Agents
Proteins

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Hayashi, T., McMahon, H., Yamasaki, S., Binz, T., Hata, Y., Südhof, T. C., & Niemann, H. (1994). Synaptic vesicle membrane fusion complex: Action of clostridial neurotoxins on assembly. EMBO Journal, 13(21), 5051-5061.

Synaptic vesicle membrane fusion complex : Action of clostridial neurotoxins on assembly. / Hayashi, Tetsuya; McMahon, Harvey; Yamasaki, Shinji; Binz, Thomas; Hata, Yutaka; Südhof, Thomas C.; Niemann, Heiner.

In: EMBO Journal, Vol. 13, No. 21, 23.11.1994, p. 5051-5061.

Research output: Contribution to journalArticle

Hayashi, T, McMahon, H, Yamasaki, S, Binz, T, Hata, Y, Südhof, TC & Niemann, H 1994, 'Synaptic vesicle membrane fusion complex: Action of clostridial neurotoxins on assembly', EMBO Journal, vol. 13, no. 21, pp. 5051-5061.
Hayashi T, McMahon H, Yamasaki S, Binz T, Hata Y, Südhof TC et al. Synaptic vesicle membrane fusion complex: Action of clostridial neurotoxins on assembly. EMBO Journal. 1994 Nov 23;13(21):5051-5061.
Hayashi, Tetsuya ; McMahon, Harvey ; Yamasaki, Shinji ; Binz, Thomas ; Hata, Yutaka ; Südhof, Thomas C. ; Niemann, Heiner. / Synaptic vesicle membrane fusion complex : Action of clostridial neurotoxins on assembly. In: EMBO Journal. 1994 ; Vol. 13, No. 21. pp. 5051-5061.
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