汤姆辛与 Munc18 和 Munc13 协调指导 SNARE 复合物的形成。
Tomosyn guides SNARE complex formation in coordination with Munc18 and Munc13.
机构信息
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
出版信息
FEBS Lett. 2018 Apr;592(7):1161-1172. doi: 10.1002/1873-3468.13018. Epub 2018 Mar 13.
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/α-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.
作为 SNARE 结合蛋白，汤姆辛已被报道通过将突触融合蛋白 1 和 SNAP-25 捕获到非融合产物中，从而负调控突触胞吐，阻止突触融合蛋白 2 的进入，这引发了一个问题，即 SNARE 复合物是如何组装的。在这里，我们研究了汤姆辛在 SNARE 复合物形成和 SNARE 介导的囊泡融合中的新功能。在 NSF/α-SNAP 的辅助下，突触融合蛋白 1 逃脱了汤姆辛的抑制，组装成 Munc18-1/突触融合蛋白 1 复合物。然后，Munc13-1 以一种特异于突触融合蛋白 2 但抵抗汤姆辛的方式催化突触融合蛋白 1 从 Munc18-1/突触融合蛋白 1 复合物向 SNARE 复合物的转移。我们的数据表明，汤姆辛以一种易于受 Munc18-1 和 Munc13-1 严格调控的方式确保 SNARE 组装。
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