The actin-severing activity of cofilin is exerted by the interplay of three distinct sites on cofilin and essential for cell viability
The actin-severing activity of cofilin is exerted by the interplay of three distinct sites on cofilin and essential for cell viability
复制标题
DOI：
10.1042/bj20020231
复制
发表时间：
2002-07-01
影响因子：
4.1
通讯作者：
Yahara, L
中科院分区：
文献类型：
--
作者：
Moriyama, K;Yahara, L
Cofilin/肌动蛋白解聚因子是肌动蛋白动力学的重要和保守的调节剂。Cofilin以单体或丝状形式与肌动蛋白结合，切断并解聚肌动蛋白丝，并加速其粉碎。在肌动蛋白为基础的运动中，F-肌动蛋白的高周转率似乎主要是由cofilin介导的定向亚基释放的加速驱动的，但很少由细丝的碎片化驱动。另一方面，cofilin的免疫切断功能似乎与细胞的健康生长有关。本研究我们已经表征了猪cofilin的三种突变体，以阐明cofilin的切割活性的分子机制。第一种突变体既不能与肌动蛋白丝结合，也不能切断它们，但它有效地加速了它们的旋转和定向亚基释放。第二个突变体绑定到肌动蛋白丝，但未能切断他们和干扰鬼笔环肽结合到细丝。第三个突变体可以与肌动蛋白丝和切断他们，虽然与一个非常降低的功效，在这些突变蛋白，只有最后一个能够拯救Deltacof 1酵母细胞和诱导厚肌动蛋白束在哺乳动物细胞过表达。因此。切丝蛋白的肌动蛋白切断活性是其生命功能中的基本要素，并建议通过切丝蛋白的至少三个不同位点的合作来发挥。
Cofilin/actin-depolymerizing factor is an essential and conserved modulator of actin dynamics. Cofilin binds to actin in either monomeric or filamentous form, severs and depolymerizes actin filaments, and speeds up their treadmilling. A high turnover rate of F-actin in actin-based motility seems driven largely by cofilin-mediated acceleration of directional subunit release, but little by fragmentation of the filaments. On the other hand, the filament-severing function of cofilin seems relevant for the healthy growth of cells. In this study. we have characterized three mutants of porcine cofilin to elucidate the molecular mechanism that underlies the filament-severing activity of cofilin. The first mutant could neither associate with actin filaments nor sever them, whereas it effectively accelerated their treadmilling and directional subunit release. The second mutant bound to actin filaments, but failed to sever them and to interfere with phalloidin binding to the filament. The third mutant could associate with actin filaments and sever them, although with a very reduced efficacy, Of these mutant proteins, only the last one was able to rescue Deltacof1 yeast cells and to induce thick actin bundles in mammalian cells upon overexpression. Therefore. the actin-severing activity of cofilin is an essential element in its vital function and suggested to be exerted by co-operation of at least three distinct sites of cofilin.