Open AccessSyntaxin 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,
Lei 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.