Elucidation of the spatio-temporal regulated formation mechanism of cellular actin-based structures.

在细胞中，肌动蛋白结构的形成是由肌动蛋白调节蛋白之间的相互作用来调节的。形成蛋白同源蛋白（形成蛋白）在肌动蛋白应力纤维和酵母肌动蛋白电缆的形成中发挥重要作用。在肌动蛋白进行性延伸过程中，哺乳动物的α-dia 1沿着F-肌动蛋白的长螺距螺旋旋转（螺旋旋转）。螺旋旋转可以在与肌动蛋白解聚因子cofilin对F-肌动蛋白的扭转相反的方向上对F-肌动蛋白施加扭转力。在本研究中，我们发现，mDia 1的螺旋旋转施加扭转力的F-肌动蛋白和增强抵抗cofilin的结合和丝切割活动的cofilin。此外，mDia 1的活性突变体通过其N-末端区域与细胞结构相连，诱导形成抗肌动蛋白分解的F-肌动蛋白。这些结果表明，mDia 1的螺旋旋转功能作为一种拮抗机制的cofilin活性。

In cells, the formation of actin structures is regulated by the interaction between actin regulatory proteins. Formin homology proteins (formins) play an essential role in the formation of actin stress fibers and yeast actin cables. A mammalian formin mDia1 rotates along the long-pitch helix of F-actin during processive actin elongation (helical rotation). Helical rotation may impose torsional force on F-actin in the opposite direction to the twisting of F-actin by an actin depolymerizing factor cofilin. In the present study, we revealed that helical rotation of mDia1 imposes torsional force on F-actin and enhances resistant against the cofilin binding and the filament severing activity of cofilin. In addition, an active mutant of mDia1 tethered to cellular structures through its N-terminal region induces the formation of F-actin resistant to actin disassembly. These results indicate that helical rotation of mDia1 functions as an antagonistic mechanism to the cofilin activity.