Rho GTPase-formin pairs in cytoskeletal remodelling.
Rho GTPase-formin pairs in cytoskeletal remodelling.
复制标题
细胞骨架重塑中的 Rho GTPase-formin 对。
DOI：
10.1002/047001766x.ch16
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Alberts,ArthurS
中科院分区：
文献类型：
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作者：
Eisenmann,KathrynM;Peng,Jun;Wallar,BradleyJ;Alberts,ArthurS
透明相关形成蛋白（Drfs）是肌动蛋白成核蛋白保守的Rho家族的成员，被认为在控制基因表达、细胞骨架重塑和细胞分裂的信号转导途径中充当Rho GTf 3效应子。体外研究表明，三种哺乳动物Drf蛋白mDia 1、mDia 2和mDia 3具有不同的GT3结合特异性。然而，我们目前对哺乳动物细胞信号传导中GTf-Drf伙伴关系的大部分理解是基于使用缺失其独特GTf-Binding结构域的Drfs的表达研究。我们已经采用荧光共振能量转移（FRET）和基因靶向方法来鉴定不同的GTd-fos对在细胞信号传导中的功能。这些研究使我们能够发现Drf蛋白在细胞骨架重塑中的新作用和GTP酶影响细胞骨架功能的新调控机制。我们的遗传实验强烈表明，Drfs与其他GTdR效应蛋白，包括Wiskott-Aldrich综合征基因的基因产物WASP，在细胞增殖的调节过程中合作。此外，Drf基因敲除实验表明，该家族的formin在癌症病理生理学中具有作用。
Diaphanous‐related formins (Drfs) are members of a conserved formin family of actin‐nucleating proteins and are thought to act as Rho GTPase effectors in signal transduction pathways that govern gene expression, cytoskeletal remodelling and cell division. In vitro evidence suggests that the three mammalian Drf proteins—mDia1, mDia2 and mDia3— have distinct GTPase‐binding specificities. However, much of our current understanding of GTPase‐Drf partnerships in mammalian cell signalling is based on expression studies using Drfs missing their unique GTPase‐binding domains. We have employed fluorescence resonance energy transfer (FRET) and gene targeting approaches to identify the function of different GTPase‐formin pairs in cell signalling. These studies have allowed us to uncover new roles for Drf proteins in cytoskeletal remodelling and novel regulatory mechanisms whereby GTPases influence formin function. Our genetic experiments strongly suggest that Drfs cooperate with other GTPase effector proteins, including the gene product of the Wiskott‐Aldrich syndrome gene, WASP, during the regulation of cell proliferation. Further, the Drf gene knockout experiments indicate that this family of formins has a role in cancer pathophysiology.