Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
J Biol Chem. 2010 May 21;285(21):16231-8. doi: 10.1074/jbc.M109.079236. Epub 2010 Mar 11.
Eukaryotic cells dynamically reorganize the actin cytoskeleton to regulate various cellular activities, such as cell shape change, cell motility, cytokinesis, and vesicular transport. Diaphanous-related formins (DRFs), such as Daam1 and mDia1, play central roles in actin dynamics through assembling linear actin filaments. It has been reported that the GTP-bound active Rho binds directly to DRFs and partially unleashes the intramolecular autoinhibition of DRFs. However, whether proteins other than Rho involve the regulation of the actin assembly activity of DRFs has been unclear. Here, we show that Flightless-I (Fli-I), a gelsolin family protein essential for early development, binds directly to Daam1 and mDia1. Fli-I enhances the intrinsic actin assembly activity of Daam1 and mDia1 in vitro and is required for Daam1-induced actin assembly in living cells. Furthermore, Fli-I promotes the GTP-bound active Rho-mediated relief of the autoinhibition of Daam1 and mDia1. Thus, Fli-I is a novel positive regulator of Rho-induced linear actin assembly mediated by DRFs.
真核细胞通过动态重排肌动蛋白细胞骨架来调节各种细胞活动,如细胞形状变化、细胞运动、胞质分裂和囊泡运输。果蝇同源物相关formin(DRFs),如 Daam1 和 mDia1,通过组装线性肌动蛋白丝在肌动蛋白动力学中发挥核心作用。据报道,结合 GTP 的活性 Rho 直接结合到 DRFs 上,并部分释放 DRFs 的分子内自动抑制。然而,除了 Rho 之外的蛋白质是否参与调节 DRFs 的肌动蛋白组装活性尚不清楚。在这里,我们表明,对早期发育至关重要的凝胶蛋白家族蛋白 Flightless-I(Fli-I)直接与 Daam1 和 mDia1 结合。Fli-I 增强了 Daam1 和 mDia1 的内在肌动蛋白组装活性,并且是 Daam1 诱导的活细胞中肌动蛋白组装所必需的。此外,Fli-I 促进了 GTP 结合的活性 Rho 介导的 Daam1 和 mDia1 自动抑制的释放。因此,Fli-I 是 Rho 诱导的由 DRFs 介导的线性肌动蛋白组装的新型正调节剂。
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