RhoB and the mammalian Diaphanous-related formin mDia2 in endosome trafficking

RhoB and the mammalian Diaphanous-related formin mDia2 in endosome trafficking
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DOI:
10.1016/j.yexcr.2006.10.033
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发表时间:
2007-02-01
影响因子:
3.7
通讯作者:
Alberts, Arthur S.
Alberts, Arthur S.
中科院分区:
医学3区
文献类型:
--
作者:
Wallar, Bradley J.;DeWard, Aaron D.;Alberts, Arthur S.

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Rho GTP酶和肌动蛋白丝的动态组装和拆卸已被证明在生长因子受体的内化和运输中具有关键作用。虽然所有三种哺乳动物透明相关的(mDia 1/2/3)β-GT受体效应蛋白已被定位在内体上,其肌动蛋白成核,细丝伸长和/或捆绑的作用仍然知之甚少,在细胞内运输的背景下。在RhoB(一种已知与早期和晚期内体相关的GTP酶)和mDia 2之间的功能关系研究中,我们发现:1)RhoB和mDia 2在内体上相互作用; 2)GTP酶活性-将GTP水解为GDP的能力-是RhoB控制内体动力学的能力所必需的; 3)RhoB和mDia 2控制的肌动蛋白动力学是囊泡运输所必需的。这些研究进一步表明,Rho GTP酶显著影响mDia家族形成蛋白的活性,通过调节肌动蛋白动力学驱动细胞膜重塑。(c)2006年爱思唯尔公司All rights reserved.
Rho GTPases and the dynamic assembly and disassembly of actin filaments have been shown to have critical roles in both the internalization and trafficking of growth factor receptors. While all three mammalian Diaphanous-related (mDia1/2/3) formin GTPase effector proteins have been localized on endosomes, a role for their actin nucleation, filament elongation, and/or bundling remains poorly understood in the context of intracellular trafficking. In a study of a functional relationship between RhoB, a GTPase known to associate with both early- and late-endosomes, and the formin mDia2, we show that 1) RhoB and mDia2 interact on endosomes; 2) GTPase activity-the ability to hydrolyze GTP to GDP-is required for the ability of RhoB to govern endosome dynamics; and 3) the actin dynamics controlled by RhoB and mDia2 is necessary for vesicle trafficking. These studies further suggest that Rho GTPases significantly influence the activity of mDia family formins in driving cellular membrane remodeling through the regulation of actin dynamics. (c) 2006 Elsevier Inc. All rights reserved.