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PMID: 9342384 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Disruption of syntaxin-mediated protein interactions blocks neurotransmitter secretion.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 22 ·1997-10-28 ·Pages 12186-91

O'Connor V, Heuss C, De Bello WM, Dresbach T, Charlton MP, Hunt JH, Pellegrini LL, Hodel A, Burger MM, Betz H, Augustine GJ, Schäfer T

Abstract

The membrane protein syntaxin participates in several protein-protein interactions that have been implicated in neurotransmitter release. To probe the physiological importance of these interactions, we microinjected into the squid giant presynaptic terminal botulinum toxin C1, which cleaves syntaxin, and the H3 domain of syntaxin, which mediates binding to other proteins. Both reagents inhibited synaptic transmission yet did not affect the number or distribution of synaptic vesicles at the presynaptic active zone. Recombinant H3 domain inhibited the interactions between syntaxin and SNAP-25 that underlie the formation of stable SNARE complexes in vitro. These data support the notion that syntaxin-mediated SNARE complexes are necessary for docked synaptic vesicles to fuse.

MeSH Terms
Amino Acid Sequence Animals Botulinum Toxins/pharmacology Cloning, Molecular Decapodiformes/genetics Membrane Fusion Membrane Proteins/genetics,metabolism Molecular Sequence Data Nerve Tissue Proteins/metabolism Neurotransmitter Agents/metabolism Peptide Fragments/metabolism Presynaptic Terminals/drug effects,ultrastructure Protein Binding/drug effects Qa-SNARE Proteins SNARE Proteins Sequence Analysis, DNA Sequence Homology, Amino Acid Synapses/drug effects,metabolism,ultrastructure Synaptosomal-Associated Protein 25 Vesicular Transport Proteins
Chemicals
Membrane Proteins Nerve Tissue Proteins Neurotransmitter Agents Peptide Fragments Qa-SNARE Proteins SNARE Proteins Synaptosomal-Associated Protein 25 Vesicular Transport Proteins Botulinum Toxins botulinum toxin type C
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
O'Connor V
Department of Neurochemistry, Max-Planck-Institute for Brain Research, 60528 Frankfurt, Germany.
Heuss C
De Bello W M
Dresbach T
Charlton M P
Hunt J H
Pellegrini L L
Hodel A
Burger M M
Betz H
Augustine G J
Schäfer T
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.22.12186
Published
1997-10-28
Pages
12186-91
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC23745
Subset
IM
Grants
NINDS NIH HHS · R01 NS021624 · United States
NINDS NIH HHS · NS 21624 · United States
Databases
GENBANK
Y14575
External Links
PubMed source DOI: 10.1073/pnas.94.22.12186 PMC Full Text View journal details
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