Mechanisms underlying NMDA receptor localization

描述（由申请人提供）：发育过程中突触的形成是哺乳动物大脑建立的重要步骤。蛋白质和受体进出突触的运输有助于维持体内平衡。当这种体内平衡被破坏时，诸如阿尔茨海默氏症和Rett综合征等疾病就会发生。一种特殊的受体，NMDA受体，对突触的正常功能很重要。我的初步研究表明，snapin与NMDA受体亚基NR1形成复合物，减少海马神经元单位面积树突NR1簇的数量。因此，了解这种相互作用如何发生以及它如何影响功能性NMDA受体运输是很重要的。我们的第一组实验将确定snapin的哪个部分与NR1相互作用，以及NR1的哪个剪接变体与snapin相互作用。第二组实验将确定snapin如何影响功能性NMDA受体聚类和突触定位。第三组实验将确定snapin是否影响功能性NMDA受体的细胞表面表达。综上所述，这些实验的结果将深入了解NMDA受体的运输。

DESCRIPTION (provided by applicant): Synapse formation during development is an important step in the establishment of the mammalian brain. Trafficking of proteins and receptors to and from the synapse helps to maintain homeostasis. Diseases such as Alzheimer's and Rett Syndrome occur when this homeostasis is disrupted. One particular receptor, the NMDA receptor, is important for proper functioning of the synapse. My preliminary studies suggest that snapin forms a complex with the NMDA receptor subunit NR1 and decreases the number of NR1 clusters per unit area of dendrite in hippocampal neurons. Therefore, it is important to understand how this interaction occurs and how it affects functional NMDA receptor trafficking. Our first set of experiments will determine which portion of snapin interacts with NR1 and which splice variant of NR1 interacts with snapin. The second group of experiments will determine how snapin affects functional NMDA receptor clustering and synaptic localization. The third set of experiments will determine if snapin affects cell surface expression of functional NMDA receptors. Taken together, the results from these experiments will give insight into NMDA receptor trafficking.