Abstract
During mitosis, a ring containing actin and myosin appears beneath the equatorial surface of animal cells. This ring then contracts, forms a cleavage furrow and divides the cell1,2,3, a step known as cytokinesis. The two daughter cells often remain connected by an intercellular bridge which contains a refringent structure known as the midbody4,5. How the appearance of this ring is regulated is unclear, although the small GTPase Rho, which controls the formation of actin structures6,7, is known to be essential8,9,10. Protein kinases are also thought to participate in cytokinesis1,2,3,11,12. We now show that a splice variant of a Rho target protein, named citron13, contains a protein kinase domain that is related to the Rho-associated kinases ROCK14 and ROK15,16,17, which regulate myosin-based contractility18,19,20,21. Citron kinase localizes to the cleavage furrow and midbody of HeLa cells; Rho is also localized in the midbody. We find that overexpression of citron mutants results in the production of multinucleate cells and that a kinase-active mutant causes abnormal contraction during cytokinesis. We propose that citron kinase regulates cytokinesis at a step after Rho in the contractile process.
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Acknowledgements
We thank S. Yonemura and I. Mabuchi for critically reading the manuscript and H.A. Popiel for editing it; H. Fuyuhiro and K. Nonomura for technical assistance; and T. Arai, H. Nose and K. Okuyama for secretarial assistance. This work was supported in part by a grant from the Ministry of Education, Sciences, Sports and Culture of Japan and by a grant for the Human Frontier Science Program. P.M. was supported in part by the Ciba–Geigy Foundation.
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Madaule, P., Eda, M., Watanabe, N. et al. Role of citron kinase as a target of the small GTPase Rho in cytokinesis. Nature 394, 491–494 (1998). https://doi.org/10.1038/28873
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DOI: https://doi.org/10.1038/28873
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