果蝇自噬基因Syntaxin17在突触发育中的功能研究

项目名称： 果蝇自噬基因Syntaxin17在突触发育中的功能研究

项目编号： No.31501117

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 黄洁

作者单位： 东南大学

项目金额： 20万元

中文摘要： 细胞自噬是一个由溶酶体介导的降解过程，底物被自噬体包裹运到溶酶体中进行降解。自噬与多种生物过程相关，包括胞内运输、脂类代谢、免疫应答等。SNARE家族基因Syntaxin17是重要的自噬相关基因，其编码的Syx17与Usnp、Vamp7形成复合物介导自噬体与溶酶体融合。Syx17突变果蝇神经元中自噬体大量累积，运动能力严重受损和过早死亡。我们的初步研究发现，Syx17及Usnp缺陷果蝇NMJ 6/7肌肉神经结（bouton）显著增多、发育异常，提示细胞自噬可能调控NMJ发育，但是其调控的机制不清。本项目将以果蝇为模式生物，运用分子神经生物学技术及电生理、行为学检测、电子显微镜技术等，以Syx17为切入点，研究细胞自噬在突触发育和信号传递中的功能和作用机理，为进一步调控自噬水平从而干预神经发育障碍奠定基础。

中文关键词： 细胞自噬；Syntaxin17；；神经肌肉接头；突触发育

英文摘要： Autophagy is a lysosome-mediated degradation process involving the enclosure of substrates in autophagosomes and their subsequent delivery to the lysosome for degradation. Autophagy is closely related to different kinds of biological processes, including intracellular transport, lipid metabolism, immune responses and so on. Syntaxin17 is an important autophagy-related gene belongs to SNARE family. In Drosophila Syx17 forms a complex with Usnp and Vamp7 to mediate the fusion of autophagosomes with lysosomes. Drosophila mutants Syx17 show large-scale accumulation of autophagosomes in neurons, severe locomotion defects and premature death. Our preliminary research shows that in Syx17 and Usnp deficient larva the bouton number in NMJ muscle 6/7 increases significantly and the NMJ development abnormally, indicating that autophagy may regulate NMJ development. However, the regulatory mechanism needs to be further investigated. In this project, we use Drosophila melanogaster as a model, utilize research techniques of molecular neurobiology in combination with electrophysiology, behavioral detection and electron microscope and study Syx17 as the key point to uncover the vital function and mechanism of autophagy in synaptic growth and signal transmission, in order to lay a foundation for further intervention of neurodevelopmental disorders by regulating autophagy levels.

英文关键词： autophagy;Syntaxin17;neuromuscular junction;synapse development