Role of KVS and MPS Subunits in Basic Neuronal Function

描述（由申请人提供）： 神经系统功能机制的研究是当前神经科学研究的一个主要热点。详细阐述神经系统对特定刺激的感知和反应的细节对于理解感官知觉，信息整合和认知的机制至关重要。无脊椎动物模型系统正在为这一努力做出重大贡献，因为基本神经元功能的许多细节是非常保守的。这在线虫C中尤为明显。它的相对简单性要求对整个神经系统的发育、结构和功能进行全面的描述。最近，我们克隆并表达了一个电压门控钾通道，KVS，它介导了C.神经系统。此外，我们还克隆了第一个C.秀丽隐杆线虫MinK相关肽（MiRPs）是与K+通道结合以改变其功能的小的跨膜蛋白。MPS- 1与心脏人MiRP 1和MiRP 3具有显著同源性（进一步强调了C. elegans作为模型系统来理解我们自己的生物过程），与感觉神经元中的KVS合作产生神经元钾电流IK。最近发现的这一通道复合物提出了几个问题的遗传，生理和功能的相关性。该提案的主要目的是研究KVS和MPS-1的功能。本项目将阐明钾通道在决定C. elegans神经元的兴奋性，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：通过突变性生殖系基因失活产生kvs-1和mps-1基因敲除的蠕虫。2目的：研究kvs和mps的加工、转运和亚细胞定位。3.目标：在培养和体内表征化学感觉神经元生理学，并确定KVS和MPS-1蛋白如何影响两栖类神经元的基本功能。4目的：建立C.秀丽隐杆线虫

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.