Rapid and selective binding to the synaptic SNARE complex suggests a modulatory role of complexins in neuroexocytosis.

Détails

ID Serval
serval:BIB_E1DD89FF8753
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Rapid and selective binding to the synaptic SNARE complex suggests a modulatory role of complexins in neuroexocytosis.
Périodique
Journal of Biological Chemistry
Auteur⸱e⸱s
Pabst S., Margittai M., Vainius D., Langen R., Jahn R., Fasshauer D.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
2002
Peer-reviewed
Oui
Volume
277
Numéro
10
Pages
7838-7848
Langue
anglais
Résumé
The Ca(2+)-triggered release of neurotransmitters is mediated by fusion of synaptic vesicles with the plasma membrane. The molecular machinery that translates the Ca(2+) signal into exocytosis is only beginning to emerge. The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins syntaxin, SNAP-25, and synaptobrevin are central components of the fusion apparatus. Assembly of a membrane-bridging ternary SNARE complex is thought to initiate membrane merger, but the roles of other factors are less understood. Complexins are two highly conserved proteins that modulate the Ca(2+) responsiveness of neurotransmitter release. In vitro, they bind in a 1:1 stoichiometry to the assembled synaptic SNARE complex, making complexins attractive candidates for controlling the exocytotic fusion apparatus. We have now performed a detailed structural, kinetic, and thermodynamic analysis of complexin binding to the SNARE complex. We found that no major conformational changes occur upon binding and that the complexin helix is aligned antiparallel to the four-helix bundle of the SNARE complex. Complexins bound rapidly (approximately 5 x 10(7) m(-1) s(-1)) and with high affinity (approximately 10 nm), making it one of the fastest protein-protein interactions characterized so far in membrane trafficking. Interestingly, neither affinity nor binding kinetics was substantially altered by Ca(2+) ions. No interaction of complexins was detectable either with individual SNARE proteins or with the binary syntaxin x SNAP-25 complex. Furthermore, complexin did not promote the formation of SNARE complex oligomers. Together, our data suggest that complexins modulate neuroexocytosis after assembly of membrane-bridging SNARE complexes.
Mots-clé
Adaptor Proteins, Vesicular Transport, Animals, Calcium/metabolism, Cell Membrane/metabolism, Cysteine/chemistry, Electron Spin Resonance Spectroscopy, Exocytosis, Kinetics, Membrane Proteins/metabolism, Models, Molecular, Models, Statistical, Mutagenesis, Site-Directed, Mutation, Nerve Tissue Proteins/chemistry, Nerve Tissue Proteins/metabolism, Neurons/metabolism, Protein Binding, Protein Conformation, Protein Structure, Secondary, Qa-SNARE Proteins, R-SNARE Proteins, Rats, Recombinant Proteins/metabolism, SNARE Proteins, Spectrometry, Fluorescence, Synaptosomal-Associated Protein 25, Thermodynamics, Time Factors, Vesicular Transport Proteins
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/09/2011 9:24
Dernière modification de la notice
20/08/2019 16:05
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