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The armadillo protein p0071 regulates Rho signalling during cytokinesis

Nature Cell Biology volume 8, pages 1432–1440 (2006)Cite this article

Abstract

Cytokinesis requires the spatio-temporal coordination of cell-cycle control and cytoskeletal reorganization. Members of the Rho-family of GTPases are crucial regulators of this process and assembly of the contractile ring depends on local activation of Rho signalling1,2,3,4. Here, we show that the armadillo protein p0071, unlike its relative p120ctn, is localized at the midbody during cytokinesis and is essential for cell division. Both knockdown and overexpression of p0071 interfered with normal cell growth and survival due to cytokinesis defects with formation of multinucleated cells and induction of apoptosis. This failure of cytokinesis seemingly correlated with the deregulation of Rho activity in response to altered p0071 expression. The function of p0071 in regulating Rho activity occurred through an association of p0071 with RhoA, as well as the physical and functional interaction of p0071 with Ect2, the one Rho guanine-nucleotide exchange factor (GEF) essential for cytokinesis. These findings support an essential role for p0071 in spatially regulating restricted Rho signalling during cytokinesis.

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Figure 1: p0071 associates with centrosomes, spindle poles and the midbody during the cell cycle.
Figure 2: Depletion of p0071 by shRNAs induces severe mitotic defects.
Figure 3: p0071 depletion induces downregulation of RhoA activity.
Figure 4: p0071 induces multinucleation after forced expression and interacts with RhoA.
Figure 5: p0071 associates with and functionally interacts with the Rho-GEF Ect2.

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Acknowledgements

We thank J. Achilles for expert technical assistance, and T. Magin and M. Osborn for critically reading the manuscript. This work was supported by grants from Deutsche Forschungsgemeinschaft (DFG; SFB 610 to M.H.) and the Bundesministerium für Bildung und Forschung (BMBF; Wilhelm Roux programme to M.H. and NBL3-Junior research group to S.H.).

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  1. Annika Wolf and Rene Keil: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Pathobiochemistry, Institute for Pathophysiology, Martin-Luther-University Halle, Hollystrasse 1, Halle, 06114, Germany

    Annika Wolf, Rene Keil, Oliver Götzl, Andrej Mun, Katrin Schwarze & Mechthild Hatzfeld

  2. Junior Group Posttranscriptional Gene Regulation, Martin-Luther-University Halle, ZAMED, Heinrich Damerow Str. 1, Halle, 06120, Germany

    Marcell Lederer & Stefan Hüttelmaier

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Correspondence to Mechthild Hatzfeld.

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Supplementary figures S1, S2, S3, S4 ,S5 and S6 (PDF 892 kb)

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Wolf, A., Keil, R., Götzl, O. et al. The armadillo protein p0071 regulates Rho signalling during cytokinesis. Nat Cell Biol 8, 1432–1440 (2006). https://doi.org/10.1038/ncb1504

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