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  • Original Paper
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Small GTPase RhoD suppresses cell migration and cytokinesis

Abstract

Rho family small GTPases regulate organization of the actin cytoskeleton. Among them, RhoA plays essential roles in the formation of the actin stress fibers, the associated focal adhesions, and the contractile rings necessary for cytokinesis. Recently, RhoD, a novel member of Rho family has been identified. The amino acid sequences of its effector domain is distinct from those of the other Rho family proteins, suggesting its unique cellular functions. Introduction of the constitutively active form of RhoDG26V into fibroblasts by microinjection or transfection resulted in disassembly of the actin stress fibers and the focal adhesions, whereas the dominant negative form of RhoDT31K did not affect these structures. The degree of cell migration assessed by the phagokinetic tracks on a substrate covered with gold particles was diminished by the expression of RhoDG26V but not by RhoDT31K. Thus, cytoskeletal alterations including the loss of stress fibers and focal adhesions by RhoD seems to lead to the retardation of cell migration. Transfection of RhoDG26V cDNA into cultured cells also induced multinucleation. Moreover, RhoDG26V microinjected into fertilized eggs and embryos of Xenopus laevis caused cleavage arrest only in the injected cells, and the uncleaved cells contained multiple nuclei. These results imply that RhoD does not affect nuclear division but can interfere with cytokinesis presumably by preventing the formation of the actin-based contractile ring. Enhancement of the stress fibers by RhoA or RhoA-activating lysophosphatidic acid was reversed by the transfection of RhoD cDNA. Accordingly, the cellular functions of RhoD are likely to be antagonistic to those of RhoA.

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Acknowledgements

We are grateful to Dr Shuh Narumiya for the generous gift of the C3 exoenzyme expression plasmid, to Dr Yoshimi Takai for the Cdc42 expression plasmid, and to Dr Takashi Obinata for permitting us to use laboratory facilities. This study was supported by research grants to T Endo from the Ministry of Education, Science, Sports, and Culture of Japan and from the Ministry of Health and Welfare of Japan for Nervous and Mental Disorders (8A-1). K Matsumoto is a Research Fellow of the Japan Society for the Promotion of Science.

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Tsubakimoto, K., Matsumoto, K., Abe, H. et al. Small GTPase RhoD suppresses cell migration and cytokinesis. Oncogene 18, 2431–2440 (1999). https://doi.org/10.1038/sj.onc.1202604

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