Departments of Pathology and Cell Biology, Emory University School of Medicine, Atlanta, GA, USA; Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
Departments of Pathology and Cell Biology, Emory University School of Medicine, Atlanta, GA, USA; Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
Eur J Cell Biol. 2022 Apr;101(2):151215. doi: 10.1016/j.ejcb.2022.151215. Epub 2022 Mar 15.
Tropomodulin and tropomyosin are important components of sarcomeric thin filaments in striated muscles. Tropomyosin decorates the side of actin filaments and enhances tropomodulin capping at the pointed ends of the filaments. Their functional relationship has been extensively characterized in vitro, but in vivo and cellular studies in mammals are often complicated by the presence of functionally redundant isoforms. Here, we used the nematode Caenorhabditis elegans, which has a relatively simple composition of tropomodulin and tropomyosin genes, and demonstrated that tropomodulin (unc-94) and tropomyosin (lev-11) are mutually dependent on each other in their sarcomere localization and regulation of sarcomeric actin assembly. Mutation of tropomodulin caused sarcomere disorganization with formation of actin aggregates. However, the actin aggregation was suppressed when tropomyosin was depleted in the tropomodulin mutant. Tropomyosin was mislocalized to the actin aggregates in the tropomodulin mutants, while sarcomere localization of tropomodulin was lost when tropomyosin was depleted. These results indicate that tropomodulin and tropomyosin are interdependent in the regulation of organized sarcomeric assembly of actin filaments in vivo.
原肌球蛋白和肌球蛋白是横纹肌肌原纤维中细肌丝的重要组成部分。肌球蛋白装饰在肌动蛋白丝的侧面，并增强肌球蛋白丝末端的帽状结构。它们在体外的功能关系已经得到了广泛的研究，但在哺乳动物体内和细胞水平的研究往往因功能冗余的同工型的存在而变得复杂。在这里，我们使用线虫秀丽隐杆线虫，它的肌球蛋白和肌球蛋白基因组成相对简单，并证明肌球蛋白（unc-94）和肌球蛋白（lev-11）在肌节定位和调节肌节肌动蛋白组装方面相互依赖。肌球蛋白突变导致肌节紊乱，形成肌动蛋白聚集体。然而，当肌球蛋白在肌球蛋白突变体中耗尽时，肌动蛋白聚集体的形成受到抑制。肌球蛋白在肌球蛋白突变体中错误定位到肌动蛋白聚集体，而当肌球蛋白耗尽时，肌球蛋白的肌节定位丢失。这些结果表明，在体内，肌球蛋白和肌球蛋白在调节有组织的肌节肌动蛋白组装中是相互依赖的。
