Department of Animal Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mol Biol Cell. 2010 Apr 15;21(8):1350-61. doi: 10.1091/mbc.e09-09-0829. Epub 2010 Feb 24.
Actin arginylation regulates lamella formation in motile fibroblasts, but the underlying molecular mechanisms are unknown. To understand how arginylation affects the actin cytoskeleton, we investigated the biochemical properties and the structural organization of actin filaments in wild-type and arginyltransferase (Ate1) knockout cells. We found that Ate1 knockout results in a dramatic reduction of the actin polymer levels in vivo accompanied by a corresponding increase in the monomer level. Purified nonarginylated actin has altered polymerization properties, and actin filaments from Ate1 knockout cells show altered interactions with several associated proteins. Ate1 knockout cells have severe impairment of cytoskeletal organization throughout the cell. Thus, arginylation regulates the ability of actin to form filaments in the whole cell rather than preventing the collapse of preformed actin networks at the cell leading edge as proposed in our previous model. This regulation is achieved through interconnected mechanisms that involve actin polymerization per se and through binding of actin-associated proteins.
肌动蛋白精氨酸化调节运动纤维母细胞的薄片形成，但潜在的分子机制尚不清楚。为了了解精氨酸化如何影响肌动球蛋白细胞骨架，我们研究了野生型和精氨酸转移酶（Ate1）敲除细胞中肌动蛋白丝的生化特性和结构组织。我们发现 Ate1 敲除导致肌动蛋白聚合物水平在体内显著降低，同时单体水平相应增加。纯化的非精氨酸化肌动蛋白具有改变的聚合性质，并且来自 Ate1 敲除细胞的肌动蛋白丝显示与几种相关蛋白的相互作用改变。Ate1 敲除细胞在整个细胞中严重破坏细胞骨架组织。因此，正如我们之前的模型所提出的那样，精氨酸化调节肌动蛋白在整个细胞中形成丝的能力，而不是防止预先形成的肌动蛋白网络在细胞前缘崩溃。这种调节是通过涉及肌动蛋白聚合本身以及肌动蛋白相关蛋白结合的相互关联的机制来实现的。
