Small GTPase RhoD suppresses cell migration and cytokinesis

Keisuke Tsubakimoto, Ken Matsumoto, Hiroshi Abe, Junichiro Ishii, Mutsuki Amano, Kozo Kaibuchi, Takeshi Endo

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

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 RhoD(G26V) into fibroblasts by microinjection or transfection resulted in disassembly of the actin stress fibers and the focal adhesions, whereas the dominant negative form of RhoD(T31K) 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 RhoD(G26V) but not by RhoD(T31K). 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 RhoD26V cDNA into cultured cells also induced multinucleation. Moreover, RhoD(G26V) 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.

Original languageEnglish
Pages (from-to)2431-2440
Number of pages10
JournalOncogene
Volume18
Issue number15
DOIs
Publication statusPublished - 15-04-1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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