Role of KVS and MPS Subunits in Basic Neuronal Function

神经系统功能机制的破译是当前神经科学研究的一大热点。详细阐述了 神经系统微调以感知和响应特定刺激的细节对 理解感觉知觉、信息整合和认知的机制。无脊椎动物模型系统是 对这一努力做出了重大贡献，因为基本神经功能的许多细节都非常保守。 尤其是线虫C.etegans，它的相对简单导致了全面的 对整个神经系统的发育、结构和功能的描述。最近，我们克隆了 在线虫中表达功能上介导基本神经元兴奋性的电压门控性钾通道KVS 神经系统。此外，我们还克隆了RAPS-L，第一个线虫MIRP。水貂相关多肽(MiRPs)很小 与钾离子通道相关的跨膜蛋白，以改变其功能。MPS-1，分享重要的 与人类心脏MiRP1和MiRP3的同源性(进一步强调秀丽线虫作为模型系统的重要性 为了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。最近发现的这种通道复合体提出了几个关于遗传、生理和功能的问题 关联性。这项建议的主要目的是研究KVS和MPS-1的功能。这个项目将阐明 钾通道在测定线虫神经元兴奋性中的作用 神经突起。我们的4个具体目标是： 1目的：通过突变胚系基因灭活产生KVS-1和RAPS-1基因敲除蠕虫。 2目的：探讨KVS和RAP的加工、贩运和亚定位。 3目的：研究培养和活体化学感觉神经元的生理学特征，并明确KVS和MPS-1是如何表达的。 蛋白质影响双栖类神经元的基本功能。 4目的：建立OFC超家族。雅致的MiRPS

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