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Title: Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly

Journal Article · · Nature Communications
ORCiD logo [1];  [1];  [1];  [2];  [3];  [4];  [1]
  1. Huazhong Univ. of Science and Technology, Wuhan (China)
  2. Chinese Academy of Sciences (CAS), Beijing (China)
  3. South-Central Univ. for Nationalities, Wuhan (China)
  4. Chinese Academy of Sciences (CAS), Beijing (China); Chinese Academy of Sciences, Shanghai (China)

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. Furthermore, our data suggest that Munc18-1 and Munc13-1 together serve as a functional template to orchestrate SNARE complex assembly.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
National Natural Science Foundation of China (NSFC); National Key Basic Research Program of China
Grant/Contract Number:
31670846; 31721002; 31670850; 2015CB910800
OSTI ID:
1510246
Journal Information:
Nature Communications, Vol. 10, Issue 1; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 252 works
Citation information provided by
Web of Science

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Cited By (6)

Maintaining order: COG complex controls Golgi trafficking, processing, and sorting journal August 2019
In vitro fusion of single synaptic and dense core vesicles reproduces key physiological properties journal August 2019
Structural dynamics and transient lipid binding of synaptobrevin-2 tune SNARE assembly and membrane fusion journal April 2019
Munc13-1 MUN domain and Munc18-1 cooperatively chaperone SNARE assembly through a tetrameric complex journal December 2019
Membrane bridging by Munc13-1 is crucial for neurotransmitter release journal February 2019
Structural dynamics and transient lipid binding of synaptobrevin-2 tune SNARE assembly and membrane fusion text January 2019

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