| Literature DB >> 28772123 |
Ying Lai1, Ucheor B Choi1, Jeremy Leitz1, Hong Jun Rhee2, Choongku Lee2, Bekir Altas2, Minglei Zhao1, Richard A Pfuetzner1, Austin L Wang1, Nils Brose2, JeongSeop Rhee2, Axel T Brunger3.
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.Entities:
Keywords: Munc13; Munc18; complexin; neuronal SNAREs; neurotransmitter release; plasticity; priming; synaptotagmin
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Year: 2017 PMID： 28772123 PMCID： PMC5747255 DOI： 10.1016/j.neuron.2017.07.004
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173