Calmodulin & Calmodulin Binding Domains in E-C Coupling

钙调蛋白

• 批准号: 6928096
• 负责人: George G Rodney
• 金额: $ 5.28万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2005-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6928096
• 关键词: Rana; binding sites; calcium binding protein; calcium channel; calcium flux; calmodulin; confocal scanning microscopy; fluorescence microscopy; laboratory mouse; neuromuscular transmission; protein isoforms; protein structure function; sarcoplasmic reticulum

DESCRIPTION (provided by applicant): The candidate, George Rodney, Ph.D., is a physiologist who has been funded by an Individual NRSA and is currently a Research Associate in the Department of Biochemistry & Molecular Biology at the University of Maryland. His career goal is to develop a productive, independent, extramurally funded laboratory, the focus of which will be to study the basic mechanisms of E-C coupling in both normal and pathological muscle. The proposed Mentored Research Scientist Development Award will provide the necessary professional and research skills needed to achieve these goals. The general goal of this proposal is to critically examine the role of calmodulin (CaM) and the CaM binding domains within the voltage dependent L-type Ca2+ channel (DHPR) and the skeletal muscle sarcoplasmic reticulum Ca2+ release channel (ryanodine receptor, RyR) in modulating skeletal muscle excitation-contraction coupling. Both the DHPR and RyR contain binding sites for the ubiquitous Ca2+ binding protein CaM and RyR is functionally modulated by CaM. Furthermore, recent data suggest that the mechanical coupling between the DHPR and RyR may occur, in part, through their CaM binding domains. To elucidate the role of CaM in the modulation of Ca2+ mobilization in skeletal muscle three specific aims are proposed. 1) Examine the role of calmodulin in modulating voltage activated versus Ca2+ activated SR Ca2+ release. 2) Examine the RyR isoform dependence of calmodulin's modulation of SR Ca2+ release. 3) Characterize the contribution of calmodulin binding domains within the DHPR and RyR on SR Ca2+ release and E-C coupling. This research will be conducted at the University of Maryland School of Medicine, which houses nationally and internationally renowned scientist studying Ca2+ signaling in muscle as well as state-of-the-art facilities in fluorescent confocal microscopy. The sponsor, Martin Schneider Ph.D., is an established investigator in muscle research and is the director of a NIH-NIAMS funded training program in muscle biology. Under the expert guidance of Dr. Schneider and his Advisory Committee of senior investigators Dr. Rodney will develop the necessary professional and research skills needed to lead an outstanding and productive career in skeletal muscle biology.

描述（由申请人提供）： 候选人乔治·罗德尼（George Rodney）博士是一名生理学家，他由单个NRSA资助，目前是马里兰大学生物化学与分子生物学系的研究助理。他的职业目标是开发一个富有成效的，独立的，外部资助的实验室，其重点是研究正常和病理肌肉中E-C耦合的基本机制。拟议的指导研究科学家发展奖将为实现这些目标提供必要的专业和研究技能。该提议的一般目标是批判性地检查依赖电压依赖性L型Ca2+通道（DHPR）和骨骼肌肌肉肌胞浆CA2+释放通道（Ryanodine受体，Ryr，RyR，RyR）在依赖电压依赖性L型Ca2+通道（DHPR）内的CAM结合域的作用。 DHPR和RYR都包含无处不在的Ca2+结合蛋白CAM和RYR的结合位点在功能上通过CAM调节。此外，最近的数据表明，DHPR和RYR之间的机械耦合可能部分通过其CAM结合域发生。为了阐明CAM在调节Ca2+动员在骨骼肌中的作用，提出了三个特定目标。 1）检查钙调蛋白在调节电压激活与CA2+激活的SR Ca2+释放中的作用。 2）检查钙调蛋白对SR Ca2+释放的调节的RYR同工型依赖性。 3）表征DHPR内和RYR中钙调蛋白结合域对SR Ca2+释放和E-C耦合的贡献。这项研究将在马里兰大学医学院进行，该学院在国内和国际知名的科学家中设有肌肉中的CA2+信号传导以及荧光共聚焦显微镜的最先进设施。赞助商马丁·施耐德（Martin Schneider）博士是肌肉研究的既定研究者，并且是NIH-NIAMS资助的肌肉生物学培训计划的主任。在施耐德博士和他的高级调查员咨询委员会的专家指导下，Rodney博士将开发领导骨骼肌生物学领域杰出和富有成效的职业所需的必要专业和研究技能。