Muscle Protein Complex Assembly and Maintenance

肌肉蛋白复合物的组装和维护

• 批准号: RGPIN-2017-05268
• 负责人: Pilgrim, David
• 金额: $ 2.04万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629058
• 关键词: Muscle; Protein; Complex; Assembly; Maintenance

The contractile sarcomere of striated muscle is one of the most complex cellular protein assemblies, and we have studied the major components for decades. In contrast, the precise steps in the assembly of sarcomeres, as well as the homeostatic processes that maintain them during activity are poorly understood at the cellular or molecular level in any system. We know the components of muscle, but little about how they are assembled, or disassembled following damage. Quality control (QC) regulation of protein folding and homeostasis, as well as staged assembly of proteins in time and space, is critically important. Our program is to understand the molecular pathways that assemble and maintain the sarcomere, or allow repair or regeneration after damage. The focus of this proposal will be on the transcriptional control networks that regulate synthesis of sarcomere components, the posttranscriptional QC regulation of thick filament assembly, and the coordination between the two during normal development, as well as when the structure of the sarcomere is perturbed by genetic lesion. The aims are:

横纹肌收缩肌节是最复杂的细胞蛋白质组装体之一，我们对它的主要成分进行了几十年的研究。相比之下，在任何系统中，在细胞或分子水平上对肌节组装的精确步骤以及在活动期间维持它们的稳态过程知之甚少。我们知道肌肉的组成部分，但很少知道它们是如何组装的，或者在受损后如何分解。蛋白质折叠和稳态的质量控制（QC）调节，以及蛋白质在时间和空间上的分阶段组装，是至关重要的。我们的计划是了解组装和维持肌节的分子途径，或允许损伤后的修复或再生。该建议的重点将是转录控制网络，调节合成的肌节组件，转录后QC调节粗丝组装，和两者之间的协调在正常发育过程中，以及当肌节的结构被遗传病变扰动。其目标是：