华中科技大学马聪研究小组报道了Munc18调节syntaxin相分离促进胞吐。相关论文于2025年11月24日发表在《自然—神经科学》杂志上。

本文在体外和体内研究了光遗传控制合成酶迁巢，作为光诱导的功能获得实验，研究团队发现光增强的迁巢减少了自发迁巢和触发的囊泡迁巢，这损害了合成酶迁巢行为。syntaxin的SNARE结构域的液-液相分离（LLPS）诱导了Clthemter的形成。对于调节机制，Munc18可以改变syntaxin的构象，其作用是减少LLPS对clthemter的形成，从而促进活性syntaxin。这些结果表明，胞吐调节涉及LLPS诱导的syntaxin clthemters，作为syntaxin储存库，Munc18从中捕获syntaxin单体形成syntaxin - Munc18复合物，为有效的syntaxin提供条件。

研究人员表示，可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）蛋白合成蛋白介导神经元胞外分泌，并在质膜上自组装成大细胞。这些细胞的形成和功能，以及它们是促进还是抑制突触-囊泡融合，目前尚不清楚。

附：英文原文

Title: Munc18 modulates syntaxin phase separation to promote exocytosis

Author: Pei, Qing, Chen, Qixin, Tian, Zhiqi, Zhu, Le, Chen, Yang, Gong, Jihong, Wang, Shen, Xiang, Yijuan, Khamo, John S., Fan, Jiaqi, Rong, Yi, Yu, Yi, Qin, Yuyang, Wu, Shiping, Faragalla, Youssef, Cao, Peng, Zhang, Kai, Lai, Ying, Wu, Ling-Gang, Ma, Cong, Yang, Xiaofei, Diao, Jiajie

Issue&Volume: 2025-11-24

Abstract: The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein syntaxin mediates neuronal exocytosis and self-assembles into large clusters in the plasma membrane. The formation and function of these clusters, and whether they promote or inhibit synaptic-vesicle fusion, remain unclear. Here using optogenetic control of syntaxin clustering in vitro and in vivo, as a light-inducible gain-of-function assay, we show that light-enhanced clustering reduces both spontaneous and triggered vesicle fusion, and this impairs mouse hunting behavior. Cluster formation is induced by liquid–liquid phase separation (LLPS) of the SNARE domain of syntaxin. For the regulatory mechanism, Munc18, which is known to alter syntaxin conformation, acts to reduce LLPS for cluster formation, thereby promoting active syntaxin. These results suggest that exocytosis regulation involves LLPS-induced syntaxin clusters that serve as a syntaxin reservoir from which Munc18 captures syntaxin monomers to form a syntaxin–Munc18 complex, setting the stage for efficient fusion.

DOI: 10.1038/s41593-025-02140-9

Source: https://www.nature.com/articles/s41593-025-02140-9