Synapsin III偶联突触前囊泡释放回收的双重调控作用及其机制研究

突触传递作为神经网络功能的基本单元，是神经系统正常运作的基础。突触囊泡作为神经递质的载体，其有序的循环机制，是维持有效突触传递的保障。Synapsin蛋白广泛存在于神经末梢，其中Synapsin I和II参与调控囊泡释放，但不影响囊泡回收，而对Synapsin III的功能并不清楚，仅有的研究也有争议。申请人利用synapsin III基因敲低小鼠，发现其抑制突触前钙电流以及神经囊泡释放，降低囊泡回收速率，显示Synapsin III可能具有调控囊泡释放和回收的双重作用。本课题利用synapsin III基因敲低/敲除小鼠，通过高精度膜片钳和荧光标记技术，在脑干花萼状突触和海马培养神经元上，研究Synapsin III偶联突触前囊泡胞吐/胞吞的精细动力学调控及其内在分子细胞机制。本课题的研究为揭示Synapsin III在囊泡循环中的双重调控机制提供全新认识，为相关神经疾病提供机制参考。

Synaptic transmission, which is the fundamental building block of the neural network, maintains the basic function of the nervous system. Synaptic vesicles serve as carriers of neurotransmitter at the presynaptic terminals, and the efficient coupling between vesicle exocytosis and endocytosis is critical in maintaining synaptic transmission. Synapsins, a family of neuron-specific phosphoproteins, localize abundantly at nerve terminals, in which they interact with synaptic vesicles. Synapsin I and II have been shown to regulate vesicle exocytosis but not endocytosis at nerve terminals. The function of Synapsin III is poorly understood and the very few studies so far are controversial. In synapsin III knock down mice the applicant found that the presynaptic calcium current was inhibited，exocytosis was reduced and endocytosis was also slowed down，suggesting a dual role in regulating exo-endoytosis of Synapsin III. This project will use high temporal resolution patch clamp technique combining fluorescent imaging at the calyces and cultured hippocampal neurons to study how Synapsin III regulates presynaptic exo-endocytosis at presynaptic terminals and its underlying mechanism. This study will provide new mechanisms of the dual role of Synapsin III in mediating the coupling between exocytosis and endocytosis at conventional synapses, and new insights into related neurological disorders.