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 and Cong Ma ()
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Shen Wang: Huazhong University of Science and Technology
Yun Li: Huazhong University of Science and Technology
Jihong Gong: Huazhong University of Science and Technology
Sheng Ye: Chinese Academy of Sciences
Xiaofei Yang: South-Central University for Nationalities
Rongguang Zhang: Chinese Academy of Sciences
Cong Ma: Huazhong University of Science and Technology

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-018-08028-6

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