Cell type-specific regulation of RhoA activity during cytokinesis

Hisayoshi Yoshizaki, Yusuke Ohba, Maria Carla Parrini, Natalia Dulianinova, Anne R. Bresnick, Naoki Mochizuki, Michiyuki Matsuda

Research output: Contribution to journalArticle

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Abstract

Rho family GTPases play pivotal roles in cytokinesis. By using probes based on the principle of fluorescence resonance energy transfer (FRET), we have shown that in HeLa cells RhoA activity increases with the progression of cytokinesis. Here we show that in Rat1A cells RhoA activity remained suppressed during most of the cytokinesis. Consistent with this observation, the expression of C3 toxin inhibited cytokinesis in HeLa cells but not in Rat1A cells. Furthermore, the expression of a dominant negative mutant of Ect2, a Rho GEF, or Y-27632, an inhibitor of the Rho-dependent kinase ROCK, inhibited cytokinesis in HeLa cells but not in Rat1A cells. In contrast to the activity of RhoA, the activity of Rac1 was suppressed during cytokinesis and started increasing at the plasma membrane of polar sides before the abscission of the daughter cells in both HeLa and RatlA cells. This type of Rac1 suppression was shown to be essential for cytokinesis because a constitutively active mutant of Rac1 induced a multinucleated phenotype in both HeLa and Rat1A cells. Moreover, the involvement of MgcRacGAP/CYK-4 in this suppression of Hac1 during cytokinesis was shown by the use of a dominant negative mutant. Because ML-7, an inhibitor of myosin light chain kinase, delayed the cytokinesis of Rat1A cells and because Pak, a Rac1 effector, is known to suppress myosin light chain kinase, the suppression of the Rac1-Pak pathway by MgcRacGAP may play a pivotal role in the cytokinesis of Rat1A cells.

Original languageEnglish (US)
Pages (from-to)44756-44762
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number43
DOIs
StatePublished - Oct 22 2004

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Myosin-Light-Chain Kinase
Cytokinesis
GTP Phosphohydrolases
Cell membranes
HeLa Cells
Phosphotransferases
rho-Associated Kinases
rho GTP-Binding Proteins
Fluorescence Resonance Energy Transfer
Cell Membrane
Y 27632
ML 7

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cell type-specific regulation of RhoA activity during cytokinesis. / Yoshizaki, Hisayoshi; Ohba, Yusuke; Parrini, Maria Carla; Dulianinova, Natalia; Bresnick, Anne R.; Mochizuki, Naoki; Matsuda, Michiyuki.

In: Journal of Biological Chemistry, Vol. 279, No. 43, 22.10.2004, p. 44756-44762.

Research output: Contribution to journalArticle

Yoshizaki, Hisayoshi ; Ohba, Yusuke ; Parrini, Maria Carla ; Dulianinova, Natalia ; Bresnick, Anne R. ; Mochizuki, Naoki ; Matsuda, Michiyuki. / Cell type-specific regulation of RhoA activity during cytokinesis. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 43. pp. 44756-44762.
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