CAPS-1调控突触囊泡分泌的结构和功能机制研究

CAPS-1作为一类含有多结构域的突触前膜蛋白，在突触囊泡分泌中发挥重要功能，它与Munc13-1一起协同调控突触囊泡的拴系、锚定和启动过程。我们前期研究阐明了Munc13-1在突触分泌中的功能机制。然而，CAPS-1的相关调控分子机制一直不清楚。在本项目中，首先，拟解析CAPS-1全长及其重要结构域的分子结构；其次，拟寻找和鉴定CAPS-1在突触前膜的相互作用蛋白，研究它们的相互作用的关系网络和功能关系，重点阐释CAPS-1和Munc13-1的相互作用，空间定位和上下游调控关系；最后，拟研究CAPS-1和Munc13-1如何协同SNARE蛋白和磷脂分子，共同调控突触分泌完成的功能机制。

CAPS-1, as an important multiple-domain protein that resides at the presynaptic terminal, plays an essential function in synaptic exocytosis. CAPS-1 works together with Munc13-1 to regulate vesicle tethering, docking and priming. Our previous work has elucidated the functional mechanism of Munc13-1 in synaptic exocytosis, however, the working mechanism of CAPS-1 has been unclear. In this project, we plan to explore the mechanism by which CAPS-1 regulates exocytosis. First, we aim to solve the molecular structures of CAPS-1 full length and its functional domains. Second, we aim to screen and identify potential CAPS-1-binding proteins, depict the binding network, and elucidate the functional relevance. In particular, we will emphasize on studying the interaction, colocalization, and functional interplay between CAPS-1 and Munc13-1. Third, we aim to reveal the mechanism how CAPS-1 and Munc13-1 work in concert with the SNARE proteins and the membrane lipids to regulate synaptic vesicle fusion.