Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly
Shen Wang, Yun Li, Jihong Gong, Sheng Ye, Xiaofei Yang, Rongguang Zhang & Cong Ma
Abstract
The transition of the Munc18-1/syntaxin-1 complex to the SNARE complex, a key step involved in exocytosis, is regulated by Munc13-1, SNAP-25 and synaptobrevin-2, but the underlying mechanism remains elusive. Here, we identify an interaction between Munc13-1 and the membrane-proximal linker region of synaptobrevin-2, and reveal its essential role in transition and exocytosis. Upon this interaction, Munc13-1 not only recruits synaptobrevin-2-embedded vesicles to the target membrane but also renders the synaptobrevin-2 SNARE motif more accessible to the Munc18-1/syntaxin-1 complex. Afterward, the entry of SNAP-25 leads to a half-zippered SNARE assembly, which eventually dissociates the Munc18-1/syntaxin-1 complex to complete SNARE complex formation. Our data suggest that Munc18-1 and Munc13-1 together serve as a functional template to orchestrate SNARE complex assembly.
附件下载：
Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly, Nature Comm, 08 Jan 2019
Nature Communications, 08 January, 2019， DOI: http://dx.doi.org/10.1038/s41467-018-08028-6
Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly
Shen Wang, Yun Li, Jihong Gong, Sheng Ye, Xiaofei Yang, Rongguang Zhang & Cong Ma
Abstract
The transition of the Munc18-1/syntaxin-1 complex to the SNARE complex, a key step involved in exocytosis, is regulated by Munc13-1, SNAP-25 and synaptobrevin-2, but the underlying mechanism remains elusive. Here, we identify an interaction between Munc13-1 and the membrane-proximal linker region of synaptobrevin-2, and reveal its essential role in transition and exocytosis. Upon this interaction, Munc13-1 not only recruits synaptobrevin-2-embedded vesicles to the target membrane but also renders the synaptobrevin-2 SNARE motif more accessible to the Munc18-1/syntaxin-1 complex. Afterward, the entry of SNAP-25 leads to a half-zippered SNARE assembly, which eventually dissociates the Munc18-1/syntaxin-1 complex to complete SNARE complex formation. Our data suggest that Munc18-1 and Munc13-1 together serve as a functional template to orchestrate SNARE complex assembly.
文章链接：https://www.nature.com/articles/s41467-018-08028-6