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

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...

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Autores principales: Wang, Shen, Li, Yun, Gong, Jihong, Ye, Sheng, Yang, Xiaofei, Zhang, Rongguang, Ma, Cong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325239/
https://www.ncbi.nlm.nih.gov/pubmed/30622273
http://dx.doi.org/10.1038/s41467-018-08028-6
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author Wang, Shen
Li, Yun
Gong, Jihong
Ye, Sheng
Yang, Xiaofei
Zhang, Rongguang
Ma, Cong
author_facet Wang, Shen
Li, Yun
Gong, Jihong
Ye, Sheng
Yang, Xiaofei
Zhang, Rongguang
Ma, Cong
author_sort Wang, Shen
collection PubMed
description 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.
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spelling pubmed-63252392019-01-10 Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly Wang, Shen Li, Yun Gong, Jihong Ye, Sheng Yang, Xiaofei Zhang, Rongguang Ma, Cong Nat Commun Article 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. Nature Publishing Group UK 2019-01-08 /pmc/articles/PMC6325239/ /pubmed/30622273 http://dx.doi.org/10.1038/s41467-018-08028-6 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wang, Shen
Li, Yun
Gong, Jihong
Ye, Sheng
Yang, Xiaofei
Zhang, Rongguang
Ma, Cong
Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly
title Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly
title_full Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly
title_fullStr Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly
title_full_unstemmed Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly
title_short Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly
title_sort munc18 and munc13 serve as a functional template to orchestrate neuronal snare complex assembly
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325239/
https://www.ncbi.nlm.nih.gov/pubmed/30622273
http://dx.doi.org/10.1038/s41467-018-08028-6
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