G Protein-Mediated Signal Transduction in Brain

G 蛋白介导的大脑信号转导

• 批准号: 6726038
• 负责人: TOHRU KOZASA
• 金额: $ 37.44万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6726038
• 关键词: G protein; SDS polyacrylamide gel electrophoresis; axon; biological signal transduction; brain; cell cell interaction; cell growth regulation; confocal scanning microscopy; dendrites; fluorescence microscopy; gene targeting; genetically modified animals; green fluorescent proteins; immunofluorescence technique; immunoprecipitation; in situ hybridization; laboratory mouse; molecular cloning; northern blottings; polymerase chain reaction; protein structure function; receptor expression; tissue /cell culture; western blottings; yeast two hybrid system; G protein; SDS polyacrylamide gel electrophoresis; axon; biological signal transduction; brain; cell cell interaction; cell growth regulation; confocal scanning microscopy; dendrites; fluorescence microscopy; gene targeting; genetically modified animals; green fluorescent proteins; immunofluorescence technique; immunoprecipitation; in situ hybridization; laboratory mouse; molecular cloning; northern blottings; polymerase chain reaction; protein structure function; receptor expression; tissue /cell culture; western blottings; yeast two hybrid system

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.

描述（逐字研究来自申请人的摘要）：G蛋白介导的信号 转导是细胞通信的基本机制。各种各样 通过G蛋白介导的神经递质和激素传播信号 诱导各种生理反应。 G蛋白在 脑。但是，它们在大脑中的生理功能的特征很差。 这项研究的目的是了解分子机制和 G蛋白介导的大脑中G蛋白介导的信号通路的生理功能。之中 G蛋白，GAO在大脑中高度表达。我们最近确定了小说 通过cDNA表达克隆策略的Gao，Grin I和Grin2的候选目标 使用磷酸化的GA亚基作为探针。 Grini和Grin2专门 在大脑中表达并刺激与神经突的生长 GAO的组成性活动突变体。在此提案中，我们将调查 通过Gao-Grin 1或 Grin2途径详细。我们将分析Gao-Grin的生化机制 诱导神经突生长的途径。我们将尝试理解功能 Grin 1和Grin2的域，并表征了其下流的成分。我们 还将尝试了解该途径在原发性培养中的作用 神经元。此外，我们将通过体内分析grin1或grin2的功能 生成用于grin1或grin2的转基因小鼠或基因敲除小鼠。我们将 还研究受体调节该途径的机理 激活，RGS蛋白或其他G蛋白介导的途径。