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: 7233293
• 负责人: FEDERICO SESTI
• 金额: $ 28.44万
• 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 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7233293
• 关键词: Afferent Neurons; Biological Models; Biological Process; Caenorhabditis elegans; Cardiac; Cognition; Complex; Development; Gene Silencing; Genetic; Human; Integral Membrane Protein; Invertebrates; Knock-out; Mediating; Mink; Mucopolysaccharidosis I; Nematoda; Nervous System Physiology; Nervous system structure; Neurons; Neurosciences Research; Peptides; Perception; Physiological; Physiology; Potassium; Potassium Channel; Process; Proteins; RPS27 gene; Role; Stimulus; Structure; Voltage-Gated Potassium Channel; comparative; human RPS27 protein; improved; in vivo; neuronal excitability; sensory mechanism; trafficking

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）： 破译神经系统功能的机制是当前神经科学研究的一个主要焦点。详细阐述神经系统对特定刺激进行感知和响应的细节对于理解感觉知觉、信息整合和认知的机制至关重要。无脊椎动物模型系统为这项工作做出了重大贡献，因为基本神经元功能的许多细节都得到了显着的保存。对于线虫来说尤其如此，其相对简单需要对整个神经系统的发育、结构和功能进行全面的描述。最近，我们克隆并功能表达了电压门控钾通道 KVS，它介导线虫神经系统的基本神经元兴奋性。此外，我们克隆了 mps-1，第一个线虫 MiRP。 MinK 相关肽 (MiRP) 是一种小型跨膜蛋白，与 K+ 通道结合以改变其功能。 MPS-1 与人类心脏 MiRP1 和 MiRP3 具有显着的同源性（进一步强调了秀丽隐杆线虫作为理解我们自身生物过程的模型系统的重要性），与感觉神经元中的 KVS 合作产生神经元钾电流 IK。最近对该通道复合体的发现提出了遗传、生理和功能相关性的几个问题。该提案的主要目标是研究 KVS 和 MPS-1 功能。该项目将阐明钾通道在确定秀丽隐杆线虫神经元兴奋性中的作用，并将提高我们对基本神经元过程的理解。我们的 4 个具体目标是： 1 目的：通过突变种系基因失活产生 kvs-1 和 mps-1 敲除蠕虫。 2 目的：研究 kvs 和 mps 加工、运输和亚细胞定位。 3 目的：表征培养物和体内的化学感应神经元生理学，并确定 KVS 和 MPS-1 蛋白如何影响两栖动物神经元的基本功能。 4 目的：建立线虫 MiRP 超家族。