| Literature DB >> 26572858 |
Chong Shen1, Shailendra S Rathore1, Haijia Yu1, Daniel R Gulbranson1, Rui Hua2, Chen Zhang2, Nathan E Schoppa3, Jingshi Shen1.
Abstract
The fusion of neurotransmitter-filled synaptic vesicles with the plasma membrane requires two classes of molecules-SNAP receptor (SNARE) and Sec1/Munc18 (SM) protein. Reconstitution studies suggest that the SM protein Munc18-1 promotes the zippering of trans-SNARE complexes and accelerates the kinetics of SNARE-dependent membrane fusion. However, the physiological role of this trans-SNARE-regulating function in synaptic exocytosis remains to be established. Here we first demonstrate that two mutations in the vesicle-anchored v-SNARE selectively impair the ability of Munc18-1 to promote trans-SNARE zippering, whereas other known Munc18-1/SNARE-binding modes are unaffected. In cultured neurons, these v-SNARE mutations strongly inhibit spontaneous as well as evoked neurotransmitter release, providing genetic evidence for the trans-SNARE-regulating function of Munc18-1 in synaptic exocytosis. Finally, we show that the trans-SNARE-regulating function of Munc18-1 is compromised by a mutation associated with Ohtahara Syndrome, a severe form of epilepsy.Entities:
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Year: 2015 PMID： 26572858 PMCID： PMC4668942 DOI： 10.1038/ncomms9852
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919