Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly
Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly
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Munc18 和 Munc13 作为功能模板来协调神经元 SNARE 复杂组件
DOI：
10.1038/s41467-018-08028-6
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发表时间：
2019-01-08
影响因子：
16.6
通讯作者：
Ma, Cong
中科院分区：
文献类型：
--
作者：
Wang, Shen;Li, Yun;Ma, Cong
Munc18-1/Synaxin-1复合体向SNARE复合体的转变是胞吐作用的关键步骤，受Munc13-1、SNAP-25和Synaptobrevin-2的调控，但其潜在的机制仍不清楚。在这里，我们确定了Munc13-1与突触素-2的膜-近端连接区之间的相互作用，并揭示了它在过渡和胞吐中的重要作用。在这种相互作用中，Munc13-1不仅将Synaptobrevin-2包埋的囊泡招募到靶膜上，而且还使Synaptobrevin-2陷阱基序更容易被Munc18-1/Synaxin-1复合体访问。随后，SNAP-25的进入导致了一个半拉链的圈套组装，最终解离Munc18-1/Synaxin-1复合体，完成圈套复合体的形成。我们的数据表明，Munc18-1和Munc13-1一起作为一个功能模板来协调SNARE复杂的组装。
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.