Role of KVS and MPS Subunits in Basic Neuronal Function

KVS 和 MPS 亚基在基本神经元功能中的作用

• 批准号: 6898445
• 负责人: FEDERICO SESTI
• 金额: $ 29.99万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6898445
• 关键词: Caenorhabditis elegans; developmental neurobiology; gene induction /repression; intracellular transport; neurophysiology; potassium channel; protein localization; protein protein interaction; protein structure function; protein transport; sensory mechanism; tissue /cell culture; voltage gated channel

DESCRIPTION (provided by applicant): Deciphering mechanisms of nervous system function is a major focus of current neuroscience research. Elaborating the details by which the nervous system is fine-tuned to sense and respond to specific stimuli is of critical importance for understanding mechanisms of sensory perception, information integration and cognition. Invertebrate model systems are making a significant contribution to this effort since many details of basic neuronal function are remarkably conserved. This is particularly actual with the nematode C. elegans whose comparative simplicity invites a comprehensive description of the development, structure and function of the entire nervous system. Recently, we have cloned and expressed functionally a voltage-gated potassium channel, KVS that mediates basic neuronal excitability in C. elegans nervous system. In addition we cloned mps-1, the first C. elegans MiRP. MinK Related Peptides (MiRPs) are small transmembrane proteins that associate with K+ channels to alter their function. MPS- 1 which shares significant homology with cardiac human MiRP1 and MiRP3 (further underscoring the importance of C. elegans as model system to understand our own biological processes), partners with KVS in sensory neurons to produce the neuronal potassium current IK. The recent discovery of this channel complex poses several questions of genetic, physiological and functional relevance. The broad aim of this proposal is to study KVS and MPS-1 function. This project will elucidate the role of potassium channels in determining C. elegans neuronal excitability and will improve our understanding of basic neuronal processes. Our 4 specific aims are: 1 Aim: To generate kvs-1 and mps-1 knockout worms through mutational germline gene inactivation. 2 Aim: To investigate kvs and mps processing, trafficking and subcellular localization. 3 Aim: To characterize chemosensory neuron physiology in culture and in vivo and to define how KVS and MPS-1 proteins influence amphid neuron basic function. 4 Aim: To establish the superfamily of C. elegans MiRPs.

描述（由申请人提供）：