Signaling Pathways that Regulate Synaptic Transmission

调节突触传递的信号通路

• 批准号: 6608621
• 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/6608621
• 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定义特征是高度调节且经常 细胞之间信息的快速传递。信息传输，称为 突触传播，发生在复杂的高度专业化地点（化学 突触），其作用是确定定性和定量 传递给相邻神经元的信号的特征。提议 研究试图定义和理解信号转导的性质 调节神经递质分泌的途径，这是突触前的 突触传输的组成部分。研究计划着重于 调节神经递质分泌的进化保守蛋白 模型有机体秀丽隐杆线虫：GO-GQ信号网络。三个专业 提案的一部分将古典遗传研究与多种 互补的分子和生化方法，以了解 该网络在遗传和生化水平上都起作用。第1部分描述 研究新颖的保守蛋白RIC-8的功能的策略 及其与GO-GQ网络的各种上游组件的关系。部分 2描述了各种策略，这些策略将用于研究四个“新” 在先前的遗传筛选中鉴定出的基因。这些基因似乎 编码参与适当功能的其他蛋白质 GO-GQ网络或交互途径。第3部分描述了其他遗传 以及将用于识别其他蛋白质的分子方法 GO-GQ网络的一部分或与之互动。通过发现新原则 关于如何调节突触传播，这项研究可以产生 关于神经系统如何建立，维护和修改的重要见解 行为。这些新原则最终可能适用于 研究人类神经系统疾病。