Molecular Mechanisms of Synaptic Vesicle Priming by Munc13 and Munc18.
Neuron
; 95(3): 591-607.e10, 2017 Aug 02.
Article
em En
| MEDLINE
| ID: mdl-28772123
ABSTRACT
Munc13 catalyzes the transit of syntaxin from a closed complex with Munc18 into the ternary SNARE complex. Here we report a new function of Munc13, independent of Munc18 it promotes the proper syntaxin/synaptobrevin subconfiguration during assembly of the ternary SNARE complex. In cooperation with Munc18, Munc13 additionally ensures the proper syntaxin/SNAP-25 subconfiguration. In a reconstituted fusion assay with SNAREs, complexin, and synaptotagmin, inclusion of both Munc13 and Munc18 quadruples the Ca2+-triggered amplitude and achieves Ca2+ sensitivity at near-physiological concentrations. In Munc13-1/2 double-knockout neurons, expression of a constitutively open mutant of syntaxin could only minimally restore neurotransmitter release relative to Munc13-1 rescue. Together, the physiological functions of Munc13 may be related to regulation of proper SNARE complex assembly.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vesículas Sinápticas
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Neurotransmissores
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Peptídeos e Proteínas de Sinalização Intracelular
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Proteínas SNARE
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Proteínas Munc18
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Exocitose
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Proteínas do Tecido Nervoso
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article