Gregorio C C, Weber A, Bondad M, Pennise C R, Fowler V M
Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037, USA.
Nature. 1995 Sep 7;377(6544):83-6. doi: 10.1038/377083a0.
Control of actin filament length and dynamics is important for cell motility and architecture and is regulated in part by capping proteins that block elongation and depolymerization at both the fast-growing (barbed) and slow-growing (pointed) ends. Tropomodulin is a capping protein for the pointed end of the actin filament; it is associated with the free, pointed ends of the thin filaments in striated muscle, where it is thought to bind to both tropomyosin and actin. In embryonic chick cardiac myocytes, tropomodulin assembles after the thin, as well as the thick, filaments have become organized into periodic I and A bands, suggesting that tropomodulin might be involved in maintaining actin filament length. Here we show that microinjection of an antibody that inhibits tropomodulin's pointed-end-capping activity in vitro results in a marked elongation of actin filaments from their pointed ends and a > 80% reduction in the percentage of beating cells. This demonstrates that pointed-end capping by tropomodulin is required to maintain actin filament length in vivo and that this is essential for contractile function in embryonic chick cardiac myocytes.
肌动蛋白丝长度和动力学的控制对于细胞运动性和结构很重要，并且部分受封端蛋白调节，这些封端蛋白可阻止快速生长（带刺）和缓慢生长（钝端）两端的伸长和解聚。原肌球蛋白调节蛋白是肌动蛋白丝钝端的封端蛋白；它与横纹肌中细肌丝的游离钝端相关，据认为它在那里与原肌球蛋白和肌动蛋白都结合。在胚胎鸡心肌细胞中，原肌球蛋白调节蛋白在细肌丝和粗肌丝都组织成周期性的I带和A带之后组装，这表明原肌球蛋白调节蛋白可能参与维持肌动蛋白丝的长度。在这里我们表明，显微注射一种在体外抑制原肌球蛋白调节蛋白钝端封端活性的抗体，会导致肌动蛋白丝从其钝端显著伸长，并且跳动细胞的百分比降低超过80%。这表明原肌球蛋白调节蛋白的钝端封端对于在体内维持肌动蛋白丝长度是必需的，并且这对于胚胎鸡心肌细胞的收缩功能至关重要。
