Molecular Basis of RGS Protein Function in the Striatum

纹状体中 RGS 蛋白功能的分子基础

• 批准号: 7783776
• 负责人: Kirill A. Martemyanov
• 金额: $ 11.64万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7783776
• 关键词: Address; Affect; Basal Ganglia; Behavior Control; Behavioral; Binding; Binding Proteins; Biochemical; Biological; Biological Assay; Brain; Cell membrane; Collaborations; Communities; Complex; Corpus striatum structure; Data; Development; Dopamine; Drug Addiction; Drug abuse; Employee Strikes; Family member; Future; G-Protein Signaling Pathway; GTP Binding; GTP-Binding Protein Regulators; GTP-Binding Proteins; Gene Delivery; Goals; Guanosine Triphosphate; Guanosine Triphosphate Phosphohydrolases; Hydrolysis; Image; Implant; In Vitro; Independent Scientist Award; Intervention; Kinetics; Knowledge; Laboratories; Lead; Learning; Locomotion; Mediating; Membrane; Mental disorders; Molecular; Names; National Institute of Drug Abuse; Neurologic; Neurons; Opioid; Pain; Pathway interactions; Perception; Play; Process; Protein Family; Proteins; Proteolysis; Proteomics; RGS Proteins; RNA Interference; Reaction; Regulation; Research; Research Personnel; Research Proposals; Role; Signal Pathway; Signal Transduction; Site; Specificity; Speed; Testing; Therapeutic; Validation; Viral; addiction; base; career development; density; design; drug of abuse; improved; insight; nervous system disorder; novel; postsynaptic; programs; protein complex; protein expression; protein function; protein protein interaction; public health relevance; response; reward processing

DESCRIPTION (provided by applicant): This is an application for the NIDA sponsored K02 Independent Scientist Award. The long term goal of the candidate is to elucidate the mechanisms of G protein signaling regulation in the basal ganglia as a necessary prerequisite to understanding neurological diseases and addiction and developing means of their treatment. The main focus of the research proposal is on the central regulator of opioid and dopamine G protein signaling, RGS9-2 that has been implicated in addiction and drug abuse. We have recently discovered that RGS9-2 in the striatum exists in a complex with a novel neuronal protein which we named R7 Binding Protein (R7BP). The HYPOTHESIS addressed by this proposal is that R7BP serves as a critical regulator of RGS9-2 function in the striatal neurons by controlling the expression level, localization, and activity of RGS9-2. This hypothesis will be addressed in the following SPECIFIC AIMS: 1. to determine the mechanisms by which R7BP controls expression of RGS9-2 in striatal neurons. 2. To understand the role of R7BP in the regulation of RGS9-2 catalytic activity. 3. To further characterize the molecular composition of G protein inactivating complex in striatal neurons. In addition to pursuing the research goals, the applicant plans to undertake career development activities by: (I) establishing and/or maintaining active collaborations with leading researchers focusing on drug addiction mechanisms, (II) integrating my research program into the larger community efforts to understand mechanisms of drug addiction and (III) learning cutting edge behavioral and imaging approaches to study drug addiction and implanting them to pursue the research directions in the laboratory. PUBLIC HEALTH RELEVANCE: The studies should provide an insight into the mechanisms that regulate reward processing in the basal ganglia of the brain. This knowledge will be important for better understanding of how drugs of abuse lead to addiction with the hopes for the future development of therapeutical intervention strategies.

描述（由申请人提供）：这是NIDA赞助K02独立科学家奖的申请。候选人的长期目标是阐明基底神经节中G蛋白信号调节的机制，这是理解神经系统疾病，成瘾以及发展其治疗方法的必要先决条件。研究建议的主要重点是阿片类药物和多巴胺G蛋白信号传导的中心调节剂RGS9-2，这与成瘾和药物滥用有关。我们最近发现，纹状体中的RGS9-2与一种新型神经元蛋白的复合物中存在，我们将其命名为R7结合蛋白（R7BP）。该提议提出的假设是，R7BP通过控制RGS9-2的表达水平，定位和活性来充当纹状体神经元中RGS9-2功能的关键调节剂。该假设将在以下特定目的中解决：1。确定R7BP控制纹状体神经元中RGS9-2表达的机制。 2。了解R7BP在RGS9-2催化活性调节中的作用。 3。进一步表征G蛋白在纹状体神经元中灭活复合物的分子组成。除了追求研究目标外，申请人计划通过以下申请人计划通过：（i）建立和/或与专注于药物成瘾机制的主要研究人员建立和/或保持积极的合作，（ii）将我的研究计划整合到更大的社区努力中，以理解药物成瘾的机制，（iii）学习最先进的行为和成像方法，以研究药物成瘾和提高研究指令，以实现这些指南，以实现研究指令。 公共卫生相关性：研究应提供对调节大脑基底神经节奖励处理的机制的见解。这些知识对于更好地理解滥用药物如何导致成瘾，这将非常重要，并希望未来的治疗干预策略发展。