Ca2+依赖的蛋白酶Calpain对突触后谷氨酸受体的调控机制

项目名称： Ca2+依赖的蛋白酶Calpain对突触后谷氨酸受体的调控机制

项目编号： No.31500824

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 神经、认识与心理学

项目作者： 赵国力

作者单位： 中国科学院遗传与发育生物学研究所

项目金额： 20万元

中文摘要： 神经递质受体在突触后的富集程度决定了突触传导的效率，但是神经递质受体的丰度是如何精确调控的却不清楚。我们的初步研究发现钙依赖的蛋白酶Calpain以及胞内钙离子浓度与突触后的谷氨酸受体GluRIIA蛋白量呈负相关，而对受体GluRIIB却没有明显影响。这些结果提示胞内钙信号可以特异性影响突触后受体GluRIIA蛋白表达，且Calpain很可能是介导这一调控的重要分子。本研究将从谷氨酸受体 GluRIIA蛋白量受到胞内钙浓度以及Calpain的影响入手，综合多学科交叉技术包括活体钙成像等，揭示钙浓度的变化如何影响突触后受体的蛋白表达以及相应的突触传导。钙信号是调控突触功能的关键分子，但在动物个体发育过程中，体内钙浓度变化是否影响神经递质受体蛋白表达量文献未见报道。本研究将为我们理解钙信号如何调控神经递质受体表达和突触功能提供新思路和新概念。

中文关键词： 谷氨酸受体；钙成像；神经肌肉突触；钙信号；蛋白水解酶

英文摘要： The efficiency of neurotransmission is determined by the level of neurotransmitter receptor at postsynaptic membrane. However, the molecular mechanism by which the level of neurotransmitter receptor expression at the postsynaptic membrane is regulated is poorly understood. Our preliminary data showed that the protein level of glutamate receptor IIA (GluRIIA) but not GluRIIB was negatively regulated by calcium dependent protease Calpains and the cytoplasmic calcium. These results indicate that GluRIIA protein level is regulated by cytoplasmic calcium signal and Calpains may be the executor in this process. The goal of this proposal is to understand how postsynaptic receptor protein level and the corresponding synaptic transmission are regulated by cytoplasmic calcium using multidisciplinary approaches including live calcium imaging. Calcium is crucial in regulation of synapse function. But, whether glutamate receptor protein level is regulated by calcium during normal development is unclear. This study will shed novel light on the regulation mechanism of calcium on glutamate receptors and synaptic function.

英文关键词： glutamate receptor;calcium imaging;neuromuscular junction;calcium signal;protease