Regulation of actin dynamics during myofibril assembly

肌原纤维组装过程中肌动蛋白动力学的调节

• 批准号: 7084525
• 负责人: Shoichiro Ono
• 金额: $ 22.47万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7084525
• 关键词: Caenorhabditis elegans; actin binding protein; actins; cryoelectron microscopy; cytoskeletal proteins; fluorescence microscopy; gene mutation; inhibitor /antagonist; intermolecular interaction; molecular assembly /self assembly; molecular dynamics; myofibrils; myogenesis; polymerization; protein protein interaction; protein structure function; tropomyosin; western blottings

Dynamic reorganization of actin cytoskeleton is accomplished by a coordinated regulation of assembly and disassembly of actin filaments. In multicellular organisms, various types of cells utilize different mechanisms to regulate actin filament dynamics. Especially in muscle cells, the actin cytoskeleton is differentiated into myofibrils, which are highly organized contractile apparatuses. The long-term objective of this project is to understand the mechanisms by which the actin cytoskeleton is reorganized into myofibrils during muscle development. The expected outcome of this research will provide insight into molecular basis of morphogenesis of cellular organelles. This proposed project will use the nematode Caenorhabditis elegans as a model system and explore the roles of actin depolymerizing factor (ADF)/cofilin in actin filament dynamics during muscle development. ADF/cofilin enhances actin filament dynamics by depolymerizing and severing actin filaments. In C. elegans, mutations in a gene encoding a muscle-specific ADF/cofilin isoform cause disorganized actin filaments in muscle cells. These studies have suggested that the muscle-specific ADF/cofilin is a critical factor to generate a dynamic state of actin filaments during myofibril assembly. The aims of this project are: (a) to determine the effects of the muscle-specific ADF/cofilin on actin filament dynamics in vitro, (b) to determine specific roles of severing and depolymerization by ADF/cofilin in myofibril assembly in vivo, (c) to determine the roles of modulators of ADF/cofilin.

肌动蛋白细胞骨架的动态重组是通过协调调节肌动蛋白丝的组装和拆卸来完成的。在多细胞生物中，各种类型的细胞利用不同的机制来调节肌动蛋白丝动力学。特别是在肌肉细胞中，肌动蛋白细胞骨架分化成肌原纤维，肌原纤维是高度组织化的收缩装置。本研究的长期目标是了解肌肉发育过程中肌动蛋白细胞骨架重组成肌原纤维的机制。本研究的预期结果将提供深入了解细胞器的形态发生的分子基础。本研究将以秀丽隐杆线虫为模型系统，探讨肌动蛋白解聚因子（ADF）/cofilin在肌肉发育过程中肌动蛋白丝动力学中的作用。ADF/cofilin通过解聚和切断肌动蛋白丝来增强肌动蛋白丝动力学。In C.在线虫中，编码肌肉特异性ADF/cofilin同种型的基因的突变导致肌肉细胞中肌动蛋白丝的紊乱。这些研究表明，肌肉特异性ADF/cofilin是在肌原纤维组装过程中产生肌动蛋白丝动态状态的关键因素。本研究的目的是：（a）确定肌肉特异性ADF/cofilin对体外肌动蛋白丝动力学的影响，（B）确定ADF/cofilin在体内肌原纤维组装中切断和解聚的特定作用，（c）确定ADF/cofilin调节剂的作用。