CapZ, PKC Signaling and Control of Sarcomere Function

CapZ、PKC 信号传导和肌节功能控制

• 批准号: 7207939
• 负责人: C AMELIA SUMANDEA
• 金额: $ 4.88万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-16 至 2007-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7207939
• 关键词: actins; biological signal transduction; cardiac myocytes; enzyme activity; gene mutation; heart function; laboratory mouse; microfilaments; muscle proteins; postdoctoral investigator; protein kinase C; protein localization; protein protein interaction; protein structure function; recombinant proteins; sarcomeres; tissue /cell culture; transfection /expression vector; yeast two hybrid system

DESCRIPTION (provided by applicant): Ample evidence indicates that the integrity of the Z-disc is critical to normal cardiac function and homeostasis. Linkage of cardiac dysfunction with mutations in the Z-disc proteins demonstrates this clearly. We reported recently that transgenic mice engineered to display a reduction in the Z-disc actin capping protein, CapZ, affect the myofilament response to Ca2+ and also induce alterations in PKC Z-disc localization. This evidence forms the bedrock of our overall objective to test the hypothesis that disturbances in the Z-disc protein network modulate myofilament activation via a "remote control" mechanism. In order to elucidate the role and the mechanism by which events at the Z-disc, through CapZ, influence the sarcomeric function and PKC signaling, we propose to address the following questions: Aim 1. What are the specific contributions of actin capping protein, CapZ, to myofilament function and PKC signaling? Aim 2. What are the components of CapZ - PKC signaling complexes? Aim 3. What is the role of actin capping protein, CapZ, in facilitating localization of PKC to the Z-disk? These studies will provide important information relevant to our understanding of events leading to severe cardiac dysfunction.

描述（由申请人提供）：充分的证据表明，z盘的完整性对正常心功能和体内平衡至关重要。心功能障碍与z -盘蛋白突变的联系清楚地证明了这一点。我们最近报道了转基因小鼠z -盘肌动蛋白封盖蛋白CapZ的减少，影响肌丝对Ca2+的反应，也诱导PKC z -盘定位的改变。这一证据构成了我们总体目标的基础，即测试z盘蛋白网络中的干扰通过“远程控制”机制调节肌丝激活的假设。为了阐明z盘上的事件通过CapZ影响肌合成功能和PKC信号传导的作用和机制，我们提出解决以下问题：肌动蛋白封盖蛋白CapZ对肌丝功能和PKC信号传导的具体贡献是什么？目标2。CapZ - PKC信号复合物的组成成分是什么？目标3。肌动蛋白封盖蛋白CapZ在促进PKC定位到z盘中的作用是什么？这些研究将为我们理解导致严重心功能障碍的事件提供重要信息。