PKC SUMO化修饰调控甘氨酸受体组成型内吞的机制研究

项目名称： PKC SUMO化修饰调控甘氨酸受体组成型内吞的机制研究

项目编号： No.31500835

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： 孙浩

作者单位： 上海交通大学

项目金额： 20万元

中文摘要： 甘氨酸受体（GlyR）膜转运调控对于神经元维持适当兴奋性是至关重要的，神经元兴奋性失衡会导致神经网络过度兴奋或过度抑制，引起相关神经系统疾病。目前GlyR调节型内吞和组成型内吞的调控机制知之甚少。我们的前期研究表明脊髓神经元中PKC SUMO化修饰参与调控kainate激活KA受体介导的GlyR瞬时调节型内吞。为了探讨PKC SUMO化修饰对神经元GlyR组成型内吞的调节作用及可能机制，本项目致力于揭示神经元内源性GlyR组成型内吞，并且在此现象基础上研究PKC SUMO化修饰调节GlyR磷酸化、GlyR和gephyrin蛋白结合进而调控GlyR组成型内吞通路的可能性，探讨其在甘氨酸能抑制性突触传递过程中的功能。为阐明PKC SUMO化修饰调控GlyR膜转运中组成型内吞环节的具体机制及其在神经元兴奋性调节中的作用提供新的思路。

中文关键词： 甘氨酸受体；组成型内吞；PKC；SUMO化修饰；抑制性突触传递

英文摘要： Surface trafficking of glycine receptor (GlyR) plays an important role in balancing neuronal excitability. An impairment of neuronal balance may lead to neuronal dysfunction. However, trafficking mechanisms of regulated endocytosis and constitutive endocytosis of GlyR remain unknown. Our previous results show activation of KA receptor (KAR) by kainate induces PKC deSUMOylation-dependent GlyR endocytosis. To further explore the possibility and mechanism of PKC SUMOylation participates in GlyR constitutive endocytosis, the aim of this project is to investigate whether and how GlyR constitutive endocytosis is regulated by PKC SUMOylation and explore the possible pathway that PKC SUMOylation regulates GlyR phosphorylation and the interaction between GlyR and gephyrin protein and ultimately result in GlyR constitutive endocytosis. This study will provide new insights for the role of PKC SUMOylation in regulation of GlyR constitutive endocytosis and in synapse inhibitory regulation and neuronal excitability control.

英文关键词： glycine receptor ;constitutive endocytosis;PKC SUMOylation;synapse inhibitory transmission