p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin

p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin
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DOI:
10.1093/emboj/16.11.3044
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发表时间:
1997-06-02
期刊:
影响因子:
11.4
通讯作者:
Narumiya, S
Narumiya, S
中科院分区:
生物学1区
文献类型:
--
作者:
Watanabe, N;Madaule, P;Narumiya, S

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Rho小G蛋白通过肌动蛋白细胞骨架调节细胞形态、粘附和胞质分裂。我们已经鉴定了一个蛋白p140 mDia作为Rho的下游效应子,它是果蝇透明蛋白(Drosophila transaphanous)的哺乳动物同源物,是一个含有重复的聚脯氨酸片段的formin相关蛋白家族。p140 mDia选择性结合Rho的GTP结合群,并且还结合profilin,p140 mDia、profilin和RhoA共定位于培养的成纤维细胞的铺展层中。它们还共同定位于佛波酯刺激的sMDCK 2细胞的膜皱褶中,其以Rho依赖性方式延伸这些结构。这三种蛋白质在纤连蛋白包被的珠粒诱导的吞噬杯周围募集。通过微量注射肉毒杆菌C3外切酶灭活Rho后,它们的募集不会被诱导。在COS-7细胞中过表达p140 mDia可诱导同质肌动蛋白丝的形成。这些结果表明,Rho调节肌动蛋白聚合通过靶向profilin通过pl 40 mDia下的特定质膜。
Rho small GTPase regulates cell morphology, adhesion and cytokinesis through the actin cytoskeleton, We have identified a protein, pl40mDia, as a downstream effector of Rho, It is a mammalian homolog of Drosophila diaphanous, a protein required for cytokinesis, and belongs to a family of formin-related proteins containing repetitive polyproline stretches. pl40mDia binds selectively to the GTP-bound farm of Rho and also binds to profilin, pl40mDia, profilin and RhoA are co-localized in the spreading lamellae of cultured fibroblasts. They are also co-localized in membrane ruffles of phorbol ester-stimulated sMDCK2 cells, which extend these structures in a Rho-dependent manner, The three proteins are recruited around phagocytic cups induced by fibronectin-coated beads. Their recruitment is not induced after Rho is inactivated by microinjection of botulinum C3 exoenzyme, Overexpression of pl40mDia in COS-7 cells induced homogeneous actin filament formation. These results suggest that Rho regulates actin polymerization by targeting profilin via pl40mDia beneath the specific plasma membranes.