The Rho family GTPase Rif induces filopodia through mDia2
The Rho family GTPase Rif induces filopodia through mDia2
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DOI：
10.1016/j.cub.2005.01.011
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发表时间：
2005-01-26
期刊：
影响因子：
9.2
通讯作者：
Mellor, H
中科院分区：
文献类型：
--
作者：
Pellegrin, S;Mellor, H
真核细胞产生各种特化的富含肌动蛋白的表面突起。其中包括丝状足——一种薄的、高度动态的突起，帮助细胞感知外部环境。丝状足由平行的肌动蛋白细丝组成，由肌动蛋白交联蛋白捆绑在一起。花丝的方向是在突出的尖端快速生长的“倒钩”端和在基部缓慢生长的“尖”端。延伸发生在顶端[3]的聚合，并由丝盖[4]的调节控制。Rho GTPase Cdc42是丝状足形成的关键介质，它通过结合CRIB结构域的效应物[2]来调节丝状足形成。Cdc42结合并激活WASP蛋白，进而激活肌动蛋白成核复合体Arp2/3[2]。它还结合并激活IRSp53， IRSp53将Ena/WASP家族蛋白Mena[5]招募到丝状面尖端，并保护延长的肌动蛋白丝不覆盖[4]。在此之前，我们发现了另一个Rho家族GTPase Rif，通过不需要Cdc42[6]的机制作为丝状肌突出的有效刺激物。在这里，我们描述了这两种小gtpase诱导丝状足的差异，并表明该途径中的Rif效应物是与丝状足相关的formin mDia2。因此，Rif和Cdc42代表了诱导丝状足产生结构的两种不同途径，它们具有共同和独特的性质。
Eukaryotic cells produce a variety of specialized actin-rich surface protrusions. These include filopodia-thin, highly dynamic projections that help cells to sense their external environment [1]. Filopodia consist of parallel filaments of actin, bundled by actin cross-linking proteins. The filaments are oriented with their rapidly growing "barbed" ends at the protruding tip and their slowly growing "pointed" ends at the base [2]. Extension occurs by polymerization at the tip [3] and is controlled by regulation of filament capping [4]. The Rho GTPase Cdc42 is a key mediator of filopodia formation, which it regulates through binding CRIB domain-containing effectors [2]. Cdc42 binds and activates the WASP proteins, which in turn activate the actin-nucleating complex Arp2/3 [2]. It also binds and activates IRSp53, which recruits the Ena/WASP family protein Mena [5] to the filopodial tip and protects elongating actin filaments from capping [4]. Previously, we identified another Rho family GTPase, Rif, as a potent stimulator of filopodial protrusion through a mechanism that does not require Cdc42 [6]. Here we characterize the differences between filopodia induced by these two small GTPases and show that the Rif effector in this pathway is the Diaphanous-related formin mDia2. Thus, Rif and Cdc42 represent two distinct routes to the induction of filopodia-producing structures with both shared and unique properties.