G Protein-Mediated Signal Transduction in Brain

描述(逐字摘自申请人摘要)：G蛋白介导的信号 转导是细胞通讯的基本机制。各种各样的 神经递质和激素通过G蛋白传递信号 引发各种生理反应。G蛋白在人体内高度表达 大脑。然而，它们在脑中的生理功能尚未得到很好的描述。 本研究的目的是了解其发生的分子机制，并探讨其可能的机制。 G蛋白介导的信号通路在脑中的生理功能。其中 G蛋白、Gao在脑内高度表达。我们最近确定了一部小说 Gao、GRIN I和GRIN2基因表达克隆策略的候选靶点 使用磷酸化的镓亚基作为探针。GRINI和GRIN2特别是 在脑中表达，并当与 Gao的结构性活性突变体。在这项建议中，我们将调查 Gao-GRIN 1或Or调控神经突起生长的分子机制 GRIN2途径的详细介绍。我们将分析高GRIN的生化机制 诱导轴突生长的途径。我们将尝试了解功能 GRIN1和GRIN2的结构域，并鉴定其下游组分。我们 也将试图了解这一途径在原代培养中的作用 神经元。此外，我们还将通过以下方式分析GRIN1或GRIN2在体内的功能 产生GRIN1或GRIN2的转基因小鼠或基因敲除小鼠。我们会 也探讨了受体对该途径的调节机制。 激活、RGS蛋白或其他G蛋白介导的途径。

DESCRIPTION (Verbatim from the Applicant's Abstract): G protein mediated signal transduction is a fundamental mechanism of cell communication. A variety of neurotransmitters and hormones transduce signals mediated through G proteins to induce various physiological responses. G proteins are highly expressed in brain. However their physiological function in brain is poorly characterized. The objective of this study is to understand the molecular mechanism and physiological function of G protein-mediated signaling pathways in brain. Among G proteins, Gao is highly expressed in brain. We recently identified novel candidate targets for Gao, GRIN I and GRIN2 by cDNA expression cloning strategy using phosphorylated Ga subunit as a probe. GRINI and GRIN2 are specifically expressed in brain and stimulate neurite growth when coexpressed with constitutively active mutant of Gao. In this proposal, we will investigate the molecular mechanism of the regulation of neurite growth through Gao-GRIN 1 or GRIN2 pathways in detail. We will analyze the biochemical mechanism of Gao-GRIN pathway to induce neurite growth. We will attempt to understand functional domains of GRIN 1 and GRIN2 and characterize their down stream components. We will also try to understand the role of this pathway in primary cultured neurons. In addition, we will analyze the function of GRIN1 or GRIN2 in vivo by generating transgenic mice or gene-knockout mice for GRIN1 or GRIN2. We will also investigate the mechanism of regulation of this pathway by receptor activation, RGS proteins, or by other G protein-mediated pathway.