A K+ Channel Learning Susceptibility Gene

K通道学习易感基因

• 批准号: 0842708
• 负责人: Federico Sesti
• 金额: $ 57.08万
• 依托单位: Rutgers, The State University of New Jersey-RBHS-Robert Wood
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0842708&HistoricalAwards=false
• 关键词: K+; Channel; Learning; Susceptibility; Gene

"This award is funded under the American Recovery and Reinvestment Act of 2009(Public Law 111-5)."Habituation is a form of non-associative learning in which repetition of a stimulus induces a progressive diminution of the behavioral response. The learning underlying habituation is a fundamental process of biological systems that is conserved from protozoans to humans. While habituation is well characterized at behavioral level, the molecular mechanisms which induce this form of learning have not been fully defined. In particular, it is not well understood how potassium channels, which are key players in controlling cellular excitability, contribute to this fundamental behavior. These studies are aimed at understanding the cellular and molecular mechanisms that induce habituation to mechanical stimulation, in the metazoan Caenorhabditis elegans. The principal investigator's laboratory discovered a novel gene, MPS-1, which is an accessory subunit of voltage-gated potassium channels and which possesses kinase activity. They have preliminary data that show that 1) MPS-1 forms a complex with voltage-gated K+ channel KHT-1 in the touch-sensing neurons of C. elegans and 2) that the kinase activity of MPS-1 specifically controls habituation in C. elegans through phosphorylation of KHT-1. In this project they propose to use a combination of genetic, electrophysiological measurements in dissected C. elegans neurons, confocal microscopy, optical measurements of calcium transients and animal model (i.e. mps-1 knock out worms, expression of MPS-1 variants in mps-1 knock outs etc.) studies to resolve the role of potassium currents in determining habituation to tap in C. elegans. This project might significantly advance our understanding of electrical mechanisms underlying habituation behavior because: 1) a new mechanism of K+ channel regulation will be elucidated; 2) habituation is an universal behavior exhibited by virtually all biological organisms including protozoans. Most importantly, trainees in the laboratory will receive first-rate guidance in a wide range of techniques, including but not limited to electrophysiology, genetics, biochemistry, microscopy and will be consequently very successful. In summary, the proposed research continues the commitment of the PI to provide training to all levels of students in the theory and practice of scientific research.

“该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。“习惯化是一种非联想学习的形式，其中重复刺激会导致行为反应的逐渐减少。 习惯化背后的学习是从原生动物到人类的生物系统的基本过程。 虽然习惯化在行为水平上得到了很好的表征，但诱导这种学习形式的分子机制尚未完全确定。 特别是，钾通道是控制细胞兴奋性的关键因素，它是如何促成这一基本行为的，目前还没有很好的理解。 这些研究的目的是了解的细胞和分子机制，诱导适应机械刺激，在后生动物秀丽隐杆线虫。主要研究者的实验室发现了一种新的基因MPS-1，它是电压门控钾通道的辅助亚基，具有激酶活性。 他们的初步数据显示：1）MPS-1与C. 2）MPS-1的激酶活性特异性地控制C.通过KHT-1的磷酸化作用。 在这个项目中，他们建议在解剖的C。elegans神经元，共聚焦显微镜，钙瞬变的光学测量和动物模型（即mps-1敲除蠕虫，mps-1敲除中MPS-1变体的表达等）研究解决钾电流在确定C.轻拍习惯中的作用。优雅的。这个项目可能会大大推进我们对习惯化行为背后的电机制的理解，因为：1）将阐明K+通道调节的新机制; 2）习惯化是几乎所有生物有机体（包括原生动物）都表现出的普遍行为。最重要的是，实验室的学员将在广泛的技术方面获得一流的指导，包括但不限于电生理学，遗传学，生物化学，显微镜，因此将非常成功。总之，拟议的研究继续PI的承诺，为各级学生提供科学研究理论和实践的培训。