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Molecular Mechanisms of Synaptic Vesicle Priming by Munc13 and Munc18.

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.

SUBMITTER: Lai Y

PROVIDER: S-EPMC5747255 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Molecular Mechanisms of Synaptic Vesicle Priming by Munc13 and Munc18.

Lai Ying Y Choi Ucheor B UB Leitz Jeremy J Rhee Hong Jun HJ Lee Choongku C Altas Bekir B Zhao Minglei M Pfuetzner Richard A RA Wang Austin L AL Brose Nils N Rhee JeongSeop J Brunger Axel T AT

Neuron 20170801 3

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 quadrup ...[more]

PMID: 28772123

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Munc13- and SNAP25-dependent molecular bridges play a key role in synaptic vesicle priming.

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