Tomosyn guides SNARE complex formation in coordination with Munc18 and Munc13.
Tomosyn guides SNARE complex formation in coordination with Munc18 and Munc13.
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Tomosyn 与 Munc18 和 Munc13 协调引导 SNARE 复合体的形成。
DOI：
10.1002/1873-3468.13018
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发表时间：
2018
期刊：
影响因子：
3.5
通讯作者：
Ma C
中科院分区：
文献类型：
--
作者：
Li Y;Wang S;Li T;Zhu L;Ma C
作为一种SNARE结合蛋白，tomosyn已被报道通过阻止syntaxin-1和SNAP-25进入非融合产物来负调节突触胞吐作用，该产物阻止小突触泡蛋白-2进入，这提出了如何实现SNARE复合物的组装的问题。在这里，我们已经调查了新的功能tomosyn在陷阱复合物的形成和陷阱介导的囊泡融合。在NSF/alpha-SNAP的协助下，syntaxin-1逃脱tomosyn阻滞并组装成Munc 18 -1/syntaxin-1复合物。然后，Munc 13 -1以对小突触泡蛋白-2特异但对tomosyn具有抗性的方式催化突触融合蛋白-1从Munc 18 -1/突触融合蛋白-1复合物转运至SNARE复合物。我们的数据表明，tomosyn确保SNARE组装的方式服从Munc 18 -1和Munc 13 -1的严格监管。
As a SNARE binding protein, tomosyn has been reported to negatively regulate synaptic exocytosis via arresting syntaxin-1 and SNAP-25 into a nonfusogenic product that precludes synaptobrevin-2 entry, raising the question how the assembly of the SNARE complex is achieved. Here, we have investigated new functions of tomosyn in SNARE complex formation and SNARE-mediated vesicle fusion. Assisted by NSF/alpha-SNAP, syntaxin-1 escapes tomosyn arrest and assembles into the Munc18-1/syntaxin-1 complex. Munc13-1 then catalyzes the transit of syntaxin-1 from the Munc18-1/syntaxin-1 complex to the SNARE complex in a manner specific to synaptobrevin-2 but resistant to tomosyn. Our data suggest that tomosyn ensures SNARE assembly in a way amenable to tight regulation by Munc18-1 and Munc13-1.