A Complete Survey of RhoGDI Targets Reveals Novel Interactions with Atypical Small GTPases.
A Complete Survey of RhoGDI Targets Reveals Novel Interactions with Atypical Small GTPases.
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DOI：
10.1021/acs.biochem.1c00120
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发表时间：
2021-05-18
期刊：
影响因子：
2.9
通讯作者：
Owen D
中科院分区：
文献类型：
--
作者：
Ahmad Mokhtar AMB;Ahmed SBM;Darling NJ;Harris M;Mott HR;Owen D
哺乳动物细胞中存在三种Rho家族小GTPases，最初被定义为Rho家族小GTPases的负调控因子。然而，现在公认的是，rhogdi不仅维持小gtpase的无活性gdp结合形式，而且还作为小gtpase的伴侣，将它们靶向到特定的细胞膜上并保护它们不被降解。迄今为止，对rhogdi的研究通常集中在“典型”或“经典”小gtp酶（如Rho、Rac和Cdc42亚家族成员）与广泛表达的RhoGDI-1或造血特异性RhoGDI-2之间的相互作用。关于该家族的第三个成员RhoGDI-3及其相互作用的伙伴所知较少。RhoGDI-3具有独特的n端延伸，并被发现定位于细胞质和高尔基体。RhoGDI-3已被证明可靶向RhoB和RhoG到细胞膜。为了更深入地了解RhoGDI的功能，我们进行了一项系统的研究，以确定所有可能与RhoGDI相互作用的Rho家族小gtpase。RhoGDI-1和RhoGDI-2活性相对有限，主要结合Rho和Rac亚家族成员。RhoGDI-3表现出更广泛的特异性，与Rho、Rac和Cdc42亚家族成员相互作用，但也与“非典型”小Rho gtpase如Wrch2/RhoV、Rnd2、Miro2和RhoH形成复合物。与RhoGDI-3共表达后，与GTP结合的RhoA、RhoB、RhoC、Rac1、RhoH和Wrch2/RhoV的水平下降，证实了RhoGDI-3作为这些小Rho GTP酶的负调节因子的作用。
There are three RhoGDIs in mammalian cells, which were initially defined as negative regulators of Rho family small GTPases. However, it is now accepted that RhoGDIs not only maintain small GTPases in their inactive GDP-bound form but also act as chaperones for small GTPases, targeting them to specific intracellular membranes and protecting them from degradation. Studies to date with RhoGDIs have usually focused on the interactions between the “typical” or “classical” small GTPases, such as the Rho, Rac, and Cdc42 subfamily members, and either the widely expressed RhoGDI-1 or the hematopoietic-specific RhoGDI-2. Less is known about the third member of the family, RhoGDI-3 and its interacting partners. RhoGDI-3 has a unique N-terminal extension and is found to localize in both the cytoplasm and the Golgi. RhoGDI-3 has been shown to target RhoB and RhoG to endomembranes. In order to facilitate a more thorough understanding of RhoGDI function, we undertook a systematic study to determine all possible Rho family small GTPases that interact with the RhoGDIs. RhoGDI-1 and RhoGDI-2 were found to have relatively restricted activity, mainly binding members of the Rho and Rac subfamilies. RhoGDI-3 displayed wider specificity, interacting with the members of Rho, Rac, and Cdc42 subfamilies but also forming complexes with “atypical” small Rho GTPases such as Wrch2/RhoV, Rnd2, Miro2, and RhoH. Levels of RhoA, RhoB, RhoC, Rac1, RhoH, and Wrch2/RhoV bound to GTP were found to decrease following coexpression with RhoGDI-3, confirming its role as a negative regulator of these small Rho GTPases.
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影响因子：
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作者：
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通讯作者：
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DOI：
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期刊：
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作者：
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DOI：
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发表时间：
2008-09-29
期刊：
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影响因子：
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影响因子：
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作者：
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