Flightless-I (Fli-I) regulates the actin assembly activity of diaphanous-related formins (DRFs) Daam1 and mDia1 in cooperation with active Rho GTPase.
Flightless-I (Fli-I) regulates the actin assembly activity of diaphanous-related formins (DRFs) Daam1 and mDia1 in cooperation with active Rho GTPase.
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DOI：
10.1074/jbc.m109.079236
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发表时间：
2010-05-21
期刊：
影响因子：
--
通讯作者：
Horiuchi H
中科院分区：
文献类型：
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作者：
Higashi T;Ikeda T;Murakami T;Shirakawa R;Kawato M;Okawa K;Furuse M;Kimura T;Kita T;Horiuchi H
真核细胞动态地重组肌动蛋白细胞骨架以调节各种细胞活动，如细胞形状改变、细胞运动、胞质分裂和囊泡运输。透明相关的形成蛋白（DRF），如Daam 1和mDia 1，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，GTP结合的活性Rho直接与DRF结合，并部分释放DRF的分子内自抑制。然而，除了Rho以外的蛋白质是否参与DRFs的肌动蛋白组装活性的调节还不清楚。在这里，我们表明，Flightless-I（Fli-I），凝溶胶蛋白家族蛋白质的早期发展必不可少的，直接结合Daam 1和mDia 1。Fli-I在体外增强Daam 1和mDia 1的内在肌动蛋白组装活性，并且是活细胞中Daam 1诱导的肌动蛋白组装所需的。此外，Fli-I促进GTP结合的活性Rho介导的Daam 1和mDia 1的自身抑制的缓解。因此，Fli-I是一种新的正调控Rho诱导的线性肌动蛋白组装DRFs介导。
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.