NMDA受体GluN2A亚单位酪氨酸1246位点磷酸化调控在学习记忆中的分子机制研究

学习记忆对于动物适应环境具有十分重要的意义。许多研究表明NMDA受体作为一种离子型谷氨酸受体，在突触可塑性和学习记忆中扮演着重要的角色。深入探索NMDA受体GluN2A亚单位的酪氨酸磷酸化修饰对于其在突触可塑性和学习记忆中功能的影响有助于深化我们对NMDA受体正常生理功能的认识。我们的前期研究发现GluN2A亚单位上的酪氨酸1246位点的磷酸化水平可以被突触可塑性调控，同时，该位点可能是Fyn激酶的作用位点。此外，酪氨酸1246位点对于GluN2A和Nck1蛋白的相互作用是必须的。基于上述主要结果和相关文献，我们计划综合运用一系列实验方法，以GluN2A的酪氨酸1246位点的磷酸化调控、Nck1为研究重点，探索它们在突触可塑性和学习记忆中的功能角色，从而推进我们对NMDA受体酪氨酸磷酸化在学习记忆中功能的理解。

Learning and memory are of great importance in animal adaption to environmental change. Convergent evidences from numerous studies demonstrate that NMDA receptors, which are ionotropic glutamate receptors, play an important role in synaptic plasticity, learning and memory. Deep exploration of tyrosine phosphorylation regulation of GluN2A subunit of NMDA receptor in synaptic plasticity as well as learning and memory would advance our understanding of physiological function of NMDA receptor. Our preliminary results show that phosphorylation level of tyrosine 1246 within GluN2A subunit is regulated by synaptic plasticity and possibly tyrosine 1246 is phosphorylated by Fyn kinase. Moreover, the tyrosine 1246 of GluN2A is requisite for GluN2A binding to Nck1. Based on our results and previous studies, we are planning to combine a series of methods, focusing on phosphorylation regulation of tyrosine 1246 and Nck1, to elucidate their functional roles in synaptic plasticity and memory. In general, our study will expand the complement of functional roles of tyrosine phosphorylation regulation of GluN2A-containing NMDA receptor in learning and memory.