Mechanism of actin filament turnover by severing and nucleation at different concentrations of ADF/cofilin
Mechanism of actin filament turnover by severing and nucleation at different concentrations of ADF/cofilin
复制标题
DOI：
10.1016/j.molcel.2006.08.006
复制
发表时间：
2006-10-06
期刊：
影响因子：
16
通讯作者：
Pollard, Thomas D.
中科院分区：
文献类型：
--
作者：
Andrianantoandro, Ernesto;Pollard, Thomas D.
ADF/cofilins是细胞运动过程中肌动蛋白动力学的关键调节因子，但它们的确切作用和作用机制仍不明确。隐失波显微镜直接观察肌动蛋白丝表明，cofilins从裂殖酵母和人类不增加的速度，肌动蛋白丝的尖端缩短超过ADP-肌动蛋白亚基的速率，但两个cofilins抑制伸长和亚基解离在倒刺末端。直接观察还表明，来自裂殖酵母、阿米巴和人类的cofilins在远低于其KdS的低cofilin结合密度下最佳地切断肌动蛋白丝，但在高结合密度下则不是。高浓度的cofilin使肌动蛋白组装成核。因此，cofilins在细胞中的作用将取决于活性cofilins的局部浓度：低浓度有利于切断，而高浓度有利于成核。这些结果建立了一个明确的范例肌动蛋白周转coflin细胞。
ADF/cofilins are key regulators of actin dynamics during cellular motility, yet their precise role and mechanism of action are shrouded in ambiguity. Direct observation of actin filaments by evanescent wave microscopy showed that cofilins from fission yeast and human do not increase the rate that pointed ends of actin filaments shorten beyond the rate for ADP-actin subunits, but both cofilins inhibit elongation and subunit dissociation at barbed ends. Direct observation also showed that cofilins from fission yeast, Acanthamoeba, and human sever actin filaments optimally at low-cofilin binding densities well below their KdS, but not at high binding densities. High concentrations of cofilin nucleate actin assembly. Thus, the action of cofilins in cells will depend on the local concentration of active cofilins: low concentrations favor severing, whereas high concentrations favor nucleation. These results establish a clear paradigm for actin turnover by coflin in cells.