Biphasic Effect of Profilin Impacts the Formin mDia1 Force-Sensing Mechanism in Actin Polymerization
Biphasic Effect of Profilin Impacts the Formin mDia1 Force-Sensing Mechanism in Actin Polymerization
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DOI：
10.1016/j.bpj.2017.06.012
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发表时间：
2017-07-25
影响因子：
3.4
通讯作者：
Ishiwata, Shin'ichi
中科院分区：
文献类型：
--
作者：
Kubota, Hiroaki;Miyazaki, Makito;Ishiwata, Shin'ichi
形成蛋白是调节肌动蛋白聚合动力学的力敏感蛋白。在这里，我们施加拉伸张力的调节下，个别肌动蛋白丝的肌动蛋白聚合动力学的机械响应。我们发现ADP-G-actin的拉伸张力比ATP-G-actin的拉伸张力更大程度地加速了肌动蛋白丝的伸长。G-actin的临界浓度明显降低，尤其是ADP-G-actin。两种类型的G-肌动蛋白的这些结果被复制一个简单的动力学模型，假设之间的快速平衡的前和posttranslocated状态的同源结构域二聚体。此外，profilin浓度显着改变力依赖性的加速肌动蛋白丝伸长，范围从两倍到全或无响应。即使在肌动蛋白解聚发生的条件下，几个皮牛顿的拉伸张力的应用程序触发快速肌动蛋白丝伸长。mDia 1和profilin的这种极高的力感应机制可以通过profilin的双相效应的力依赖性协调来解释;即，在拉伸张力下，被解聚效应掩盖的加速效应变得占主导地位，从而否定了后者以快速提高伸长率。我们的研究结果表明，profilin的双相效应是由机械力控制的，从而扩大了mDia 1作为肌动蛋白聚合的机械敏感调节剂的功能。
Formins are force-sensing proteins that regulate actin polymerization dynamics. Here, we applied stretching tension to individual actin filaments under the regulation of formin mDia1 to investigate the mechanical responses in actin polymerization dynamics. We found that the elongation of an actin filament was accelerated to a greater degree by stretching tension for ADP-G-actin than that for ATP-G-actin. An apparent decrease in the critical concentration of G-actin was observed, especially in ADP-G-actin. These results on two types of G-actin were reproduced by a simple kinetic model, assuming the rapid equilibrium between pre-and posttranslocated states of the formin homology domain two dimer. In addition, profilin concentration dramatically altered the force-dependent acceleration of actin filament elongation, which ranged from twofold to an all-or-none response. Even under conditions in which actin depolymerization occurred, applications of a several-piconewton stretching tension triggered rapid actin filament elongation. This extremely high force-sensing mechanism of mDia1 and profilin could be explained by the force-dependent coordination of the biphasic effect of profilin; i.e., an acceleration effect masked by a depolymerization effect became dominant under stretching tension, negating the latter to rapidly enhance the elongation rate. Our findings demonstrate that the biphasic effect of profilin is controlled by mechanical force, thus expanding the function of mDia1 as a mechanosensitive regulator of actin polymerization.