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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

基本信息

批准号：
7456213
负责人：
FEDERICO SESTI
金额：
$ 0.7万
依托单位：
UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
依托单位国家：
美国
项目类别：
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

项目摘要

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. etegans 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 raps-l, 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 raps-1 knockout worms through mutational germline gene inactivation. 2 Aim: To investigate kvs and raps processing, trafficking and subceUular 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 ofC. elegans MiRPs

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。拟订神经系统被微调以感知和响应特定刺激的细节对于理解感官知觉、信息整合和认知的机制。无脊椎动物模型系统是因为基本神经元功能的许多细节是非常保守的，所以对这一努力做出了重大贡献。这在线虫C中尤为明显。相对简单的工程，描述整个神经系统的发育、结构和功能。最近，我们克隆了在功能上表达一种电压门控钾通道，KVS，其介导C. elegans 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）是一种小分子多肽。与K +通道结合以改变其功能的跨膜蛋白。MPS- 1，与心脏人MiRP 1和MiRP 3的同源性（进一步强调了C.模式系统了解我们自己的生物过程），与感觉神经元中的KVS合作产生神经元钾当前IK。最近发现的这一通道复合体提出了几个遗传，生理和功能的问题本案无关该提案的主要目的是研究KVS和MPS-1的功能。该项目将阐明钾通道在决定C. elegans神经元的兴奋性，将提高我们对基本的理解神经突起我们的四个具体目标是： 1目的：通过突变性生殖系基因失活，获得kvs-1和raps-1基因敲除的蠕虫。 2目的：研究kvs和raps的加工、运输和细胞内定位。 3目的：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如何在体外表达。蛋白质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