G Protein-Mediated Signal Transduction in Brain

描述（逐字来自申请人的摘要）：G蛋白介导的信号 转导是细胞通讯的基本机制。各种 神经递质和激素通过G蛋白介导的信号， 引起各种生理反应。G蛋白高表达于 个脑袋然而，其在脑中的生理功能的特点是很差的。 本研究的目的是了解分子机制， G蛋白介导的信号通路在脑中的生理功能。之间 G蛋白，高在大脑中高度表达。我们最近发现了一种 通过cDNA表达克隆策略获得Gao、GRIN I和GRIN 2的候选靶标 以磷酸化Ga亚基为探针，GRINI和GRIN 2特别是 在脑中表达，当与 高的组成型活性突变体。在本建议书中，我们将调查 通过Gao-GRIN 1或GRIN 2调节神经突起生长的分子机制 GRIN 2通路详细。我们将分析Gao-GRIN的生化机制 诱导神经突生长的途径。我们将尝试理解函数 GRIN 1和GRIN 2的结构域，并表征其下游组分。我们 我们也将尝试了解这一途径在原代培养中的作用， 神经元此外，我们将通过以下方法分析GRIN 1或GRIN 2在体内的功能： 产生GRIN 1或GRIN 2的转基因小鼠或基因敲除小鼠。我们将 并探讨受体对该通路的调控机制 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.