PSD-95 PROTEIN FAMILY IN RECEPTOR CLUSTERING

描述：申请人的长期目标是了解分子 ASIS 突触功能。 由于许多神经系统疾病，如癫痫， 精神分裂症和抑郁症，都是由突触功能障碍引起的， e 在分子水平上对突触机制的理解， 了解这些疾病的基础。 突触前末梢释放的神经递质与特定的 受体打开位于突触后膜上的特定通道 . 包括感受器在内的重要的突触成分是如何在神经元中形成的， S 并且通道定位于突触膜的特定位点。 一 称为突触后密度的特殊细胞骨架结构， 参与受体/通道定位的机制。 应用程序 我已经分离出一个编码PSD-95的基因，PSD-95是突触后神经元中的一种重要蛋白质。 密度的 最近，越来越多的证据表明PSD-95蛋白是一种cru al 对于某些受体和通道在系统的离散位点的定位， ptic 膜，并且定位过程由以下之间的相互作用介导： PSD-95和受体/通道蛋白的特定结构域。 本研究旨在研究PSD-95及其同系物在细胞凋亡中的作用。 受体/通道定位。 这些高贵的PSD-95同系物有组织 特异性不同于PSD-95，表明PSD-95样家族 蛋白质可以与组织特异性蛋白质相互作用。 具体目标是 S 结果如下：（1）这些基因的mRNA和蛋白产物的组织定位 用原位杂交和免疫细胞化学方法检测。（2）Th GLGF PSD-95的结构域被证明是重要的相互作用， 受体/通道蛋白。 将产生转基因小鼠以测试是否 的 PSD-95的GLGF结构域过表达可能抑制PSD-95的受体聚集， （3）PSD-95的SH 3结构域可能与一组不同的蛋白相互作用， 移民局， 但这种可能性尚未经过测试。 他们将使用酵母双杂交 （4）GABAA β受体亚单位含有： 一 与PSD-95相互作用所必需的共有序列。 这将是T Ted 该亚基是否也可以被PSD-95蛋白聚集。

DESCRIPTION: The applicant's long term goal is to understand the molecular asis of synaptic function. Since many neurological diseases such as epilepsy, schizophrenia and depression, are caused by malfunctioning of the synapse, e understanding of synaptic mechanisms at the molecular level should provide insight into the basis of such diseases. Neurotransmitters released from the presynaptic terminals bind to specific receptors to open up specific channels localized on the postsynaptic membra . It has been a puzzle how the important synaptic components including recept s and channels become localized to specific sites of synaptic membranes. A specialized, cytoskeletal structure called postsynaptic density has been implicated in the mechanism of receptor/channel localization. The applican have isolated a gene encoding PSD-95, a prominent protein in the postsynapt density. Recently, evidence is accumulating that the PSD-95 protein is cru al for the localization of some receptors and channels at discrete sites of sy ptic membrane, and the localization process is mediated by interactions between specific domains of PSD-95 and receptor/channel proteins. The proposal is to study the roles of PSD-95 and its homologs in the receptor/channel localization. These noble PSD-95 homologs have tissue specificity distinct from PSD-95, suggesting that a family of PSD-95-like proteins may interact with tissue-specific proteins. The specific aims are s follows: (1) Tissue localization of mRNA and protein products of these gen will be examined by in situ hybridizations and immunocytochemistry, (2) Th GLGF domain of PSD-95 was shown to be important for the interaction with receptor/channel proteins. Transgenic mice will be generated to test wheth the overexpression of GLGF domain of PSD-95 might inhibit receptor clustering i vivo, (3) The SH3 domain of PSD-95 may interact with a different set of pro ins, but this possibility has not been tested. They will use a yeast two-hybrid system to search for such proteins, (4) GABAA beta receptor subunits contai a consensus sequence necessary for the interaction with PSD-95. It will be t ted whether this subunit can also be clustered by the PSD-95 protein.