Yamashiro Sawako, Cox Elisabeth A, Baillie David L, Hardin Jeff D, Ono Shoichiro
Department of Pathology and Department of Cell Biology, Emory University, Atlanta, GA 30322, USA.
J Cell Sci. 2008 Dec 1;121(Pt 23):3867-77. doi: 10.1242/jcs.040477. Epub 2008 Nov 4.
Sarcomeric organization of thin and thick filaments in striated muscle is important for the efficient generation of contractile forces. Sarcomeric actin filaments are uniform in their lengths and regularly arranged in a striated pattern. Tropomodulin caps the pointed end of actin filaments and is a crucial regulator of sarcomere assembly. Here, we report unexpected synergistic functions of tropomodulin with enhancers of actin filament dynamics in Caenorhabditis elegans striated muscle. Pointed-end capping by tropomodulin inhibited actin filament depolymerization by ADF/cofilin in vitro. However, in vivo, the depletion of tropomodulin strongly enhanced the disorganization of sarcomeric actin filaments in ADF/cofilin mutants, rather than antagonistically suppressing the phenotype. Similar phenotypic enhancements by tropomodulin depletion were also observed in mutant backgrounds for AIP1 and profilin. These in vivo effects cannot be simply explained by antagonistic effects of tropomodulin and ADF/cofilin in vitro. Thus, we propose a model in which tropomodulin and enhancers of actin dynamics synergistically regulate elongation and shortening of actin filaments at the pointed end.
横纹肌中细肌丝和粗肌丝的肌节组织对于有效产生收缩力很重要。肌节肌动蛋白丝长度一致，并以条纹状模式规则排列。原肌球蛋白封端于肌动蛋白丝的尖端，是肌节组装的关键调节因子。在此，我们报道了秀丽隐杆线虫横纹肌中原肌球蛋白与肌动蛋白丝动力学增强因子的意外协同功能。在体外，原肌球蛋白的尖端封端抑制了ADF/丝切蛋白介导的肌动蛋白丝解聚。然而，在体内，原肌球蛋白的缺失强烈增强了ADF/丝切蛋白突变体中肌节肌动蛋白丝的紊乱，而不是拮抗抑制该表型。在AIP1和丝切蛋白原的突变背景中也观察到了原肌球蛋白缺失导致的类似表型增强。这些体内效应不能简单地用体外原肌球蛋白和ADF/丝切蛋白的拮抗作用来解释。因此，我们提出了一个模型，其中原肌球蛋白和肌动蛋白动力学增强因子协同调节肌动蛋白丝在尖端的伸长和缩短。
