The trans-SNARE-regulating function of Munc18-1 is essential to synaptic   exocytosis

doi:10.1038/ncomms9852

CORC > 北京大学 > 生命科学学院

	The trans-SNARE-regulating function of Munc18-1 is essential to synaptic exocytosis
	Shen, Chong ; Rathore, Shailendra S. ; Yu, Haijia ; Gulbranson, Daniel R. ; Hua, Rui ; Zhang, Chen ; Schoppa, Nathan E. ; Shen, Jingshi
刊名	NATURE COMMUNICATIONS
	2015
关键词	INTRACELLULAR MEMBRANE-FUSION SYNTAXIN N-PEPTIDE NEUROTRANSMITTER RELEASE SEC1/MUNC18 PROTEINS VESICLE FUSION DEPENDENT MANNER STXBP1 MUTATIONS BINDING MODE SEC1 HOMOLOG IN-VITRO
DOI	10.1038/ncomms9852
英文摘要	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.; NBRPC Grant [2014CB942804]; NSFC [31222025]; NIH [R01DC006640, R01GM102217]; SCI(E); PubMed; ARTICLE; jingshi.shen@colorado.edu; 8852; 6
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/416732]
专题	生命科学学院
推荐引用方式 GB/T 7714	Shen, Chong,Rathore, Shailendra S.,Yu, Haijia,et al. The trans-SNARE-regulating function of Munc18-1 is essential to synaptic exocytosis[J]. NATURE COMMUNICATIONS,2015.
APA	Shen, Chong.,Rathore, Shailendra S..,Yu, Haijia.,Gulbranson, Daniel R..,Hua, Rui.,...&Shen, Jingshi.(2015).The trans-SNARE-regulating function of Munc18-1 is essential to synaptic exocytosis.NATURE COMMUNICATIONS.
MLA	Shen, Chong,et al."The trans-SNARE-regulating function of Munc18-1 is essential to synaptic exocytosis".NATURE COMMUNICATIONS (2015).