Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming | Zendy

Xiaoyu Yang | Zendy; Shen Wang | Zendy; Yi Sheng | Zendy; Mingshu Zhang | Zendy; Wenjuan Zou | Zendy; Lijie Wu | Zendy; Lijun Kang | Zendy; Josep Rizo | Zendy; Rongguang Zhang | Zendy; Tao Xu | Zendy; Cong Ma | Zendy

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Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming

Author(s) -

Xiaoyu Yang,

Shen Wang,

Yi Sheng,

Mingshu Zhang,

Wenjuan Zou,

Lijie Wu,

Lijun Kang,

Josep Rizo,

Rongguang Zhang,

Tao Xu,

Cong Ma

Publication year - 2015

Publication title -

nature structural and molecular biology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 9.448

H-Index - 270

eISSN - 1545-9993

pISSN - 1545-9985

DOI - 10.1038/nsmb.3038

Subject(s) - vesicle fusion , snap25 , synaptic vesicle , microbiology and biotechnology , biology , caenorhabditis elegans , vesicle , snare complex , lipid bilayer fusion , priming (agriculture) , syntaxin , kiss and run fusion , neuroscience , genetics , membrane , gene , germination , botany

UNC-13-Munc13s have a central function in synaptic-vesicle priming through their MUN domains. However, it is unclear whether this function arises from the ability of the MUN domain to mediate the transition from the Munc18-1-closed syntaxin-1 complex to the SNARE complex in vitro. The crystal structure of the rat Munc13-1 MUN domain now reveals an elongated, arch-shaped architecture formed by α-helical bundles, with a highly conserved hydrophobic pocket in the middle. Mutation of two residues (NF) in this pocket abolishes the stimulation caused by the Munc13-1 MUN domain on SNARE-complex assembly and on SNARE-dependent proteoliposome fusion in vitro. Moreover, the same mutation in UNC-13 abrogates synaptic-vesicle priming in Caenorhabditis elegans neuromuscular junctions. These results support the notion that orchestration of syntaxin-1 opening and SNARE-complex assembly underlies the central role of UNC-13-Munc13s in synaptic-vesicle priming.

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