Synaptotagmin-1通过C2B结构域调控神经突触胞吐的机制研究

在神经突触胞吐过程中，突触囊泡经历锚定、成熟和钙离子触发的膜融合3个重要阶段，迅速释放神经递质。SNARE复合物在胞吐过程中扮演着中心作用，它的动态组装调控了突触囊泡锚定、成熟和膜融合过程。除了SNARE复合物，Synaptotagmin-1 (Syt1)作为钙离子感应蛋白，通过其C2结构域（C2A和C2B）调控神经递质分泌。目前研究认为Syt1主要通过C2B结构域来加速神经突触胞吐，然而分子机制尚不清楚。我们在该研究中力图揭示C2B结构域调控突触胞吐的分子机制。具体内容包括：1，有钙和无钙环境下，分析和鉴定C2B与磷脂膜和SNARE复合物的相互作用特征；2，研究C2B如何协同Munc18-1和Munc13s共同加速SNARE复合物组装的分子机制；3，研究C2B如何引发膜形变，改变膜曲率的分子机制。以上研究有助于我们深入理解Syt1调控突触囊泡锚定、成熟和融合来加速胞吐的分子机制。

During synaptic exocytosis, synaptic vesicles undergo docking, priming and Ca2+-triggered fusion to release neurotransmitters. SNARE complex plays a central function in exocytosis and SNARE complex assembly controls vesicle docking, priming and fusion. In addition to the SNARE complex, Synaptotagmin-1 (Syt1), acting as a Ca2+ sensor, plays a key role in neurotransmitter release through its two C2 domains (c2A and C2B). It has been proposed that Syt1 promotes exocytosis mainly through its C2B domain, but the underlying mechanism is poorly understood. In this study, we sought to investigate the mechanism by which C2B domain regulates exocytosis. First, we will characterize how C2B domain interacts membranes and SNARE complex in the absence and presence of Ca2+. Second, we will investigate how C2B domain accelerates SNARE complex assembly in the presence of Munc18-1 and Munc13s. Third, we will explore how C2B bends membranes and induces membrane curvature in response to Ca2+. This work will shed light on the way in which Syt1 regulates vesicle docking, priming and fusion to promote exocytosis.