Signaling Pathways that Regulate Synaptic Transmission

调节突触传递的信号通路

• 批准号: 6539188
• 负责人: KENNETH George MILLER
• 金额: $ 27.46万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-17 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6539188
• 关键词: Caenorhabditis elegans; G protein; acetylcholine; biological signal transduction; cell cell interaction; cholinesterase inhibitors; gene expression; immunocytochemistry; immunoprecipitation; invertebrate embryology; molecular cloning; nerve /myelin protein; neural transmission; neurogenetics; neuroregulation; protein kinase C; protein localization; protein structure function; site directed mutagenesis; suppressor mutations; synapses; yeast two hybrid system

DESCRIPTION (provided by applicant): A defining feature of all nervous systems is the highly regulated and often rapid transfer of information between cells. The information transfer, known as synaptic transmission, occurs at complex, highly specialized sites (chemical synapses), whose role it is to determine both the qualitative and quantitative features of the signals that are passed on to neighboring neurons. The proposed research seeks to define, and understand the nature of, the signal transduction pathways that regulate neurotransmitter secretion, which is the presynaptic component of synaptic transmission. The research plan focuses on a network of evolutionarily conserved proteins that regulates neurotransmitter secretion in the model organism C. elegans: the Go-Gq signaling network. The three major parts of the proposal merge classical genetic studies with a variety of complementary molecular and biochemical approaches in order to understand how this network functions at both genetic and biochemical levels. Part 1 describes strategies to investigate the function of the novel, conserved protein RIC-8 and its relationship to various upstream components of the Go-Gq network. Part 2 describes a variety of strategies that will be used to investigate four "new" genes that were identified in previous genetic screens. These genes appear to encode additional proteins that are involved in the proper function of the Go-Gq network or an interacting pathway. Part 3 describes additional genetic and molecular approaches that will be used to identify other proteins that are part of, or interact with, the Go-Gq network. By discovering new principles about how synaptic transmission is regulated, this research could yield important insights into how nervous systems establish, maintain, and modify behavior. These new principles may ultimately be applicable to the investigation of human neurological disorders.

描述（由申请人提供）： 所有神经系统的一个决定性特征是高度调节且经常 细胞之间的信息快速传递。信息传递，称为 突触传递发生在复杂、高度专业化的位点（化学 突触），其作用是确定定性和定量 传递到邻近神经元的信号的特征。拟议的 研究旨在定义和理解信号转导的本质 调节神经递质分泌的途径，即突触前 突触传递的组成部分。该研究计划的重点是网络 调节神经递质分泌的进化保守蛋白 模式生物线虫：Go-Gq 信号网络。三大 该提案的部分内容将经典遗传学研究与各种 互补的分子和生化方法，以了解如何 该网络在遗传和生化水平上发挥作用。第 1 部分描述 研究新型保守蛋白 RIC-8 功能的策略 及其与 Go-Gq 网络各个上游组件的关系。部分 2 描述了将用于调查四种“新”的各种策略 在之前的基因筛选中鉴定出的基因。这些基因似乎 编码参与正常功能的其他蛋白质 Go-Gq 网络或交互路径。第 3 部分描述了额外的遗传因素 以及将用于鉴定其他蛋白质的分子方法 Go-Gq 网络的一部分或与之交互。通过发现新原理 关于突触传递如何调节，这项研究可能会产生 关于神经系统如何建立、维持和修改的重要见解 行为。这些新原则最终可能适用于 人类神经系统疾病的研究。