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Nat Cell Biol. 2015 Nov;17(11):1471-83. doi: 10.1038/ncb3251. Epub 2015 Oct 19.

Activator-inhibitor coupling between Rho signalling and actin assembly makes the cell cortex an excitable medium.

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Laboratory of Cell and Molecular Biology, Graduate Program in Cell and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Centre for Synthetic and Systems Biology, University of Edinburgh, Edinburgh EH9 3BF, UK.
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Boston, Massachusetts  02142, USA.
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48190, USA.
Oregon Institute of Marine Biology, University of Oregon, Charleston, Oregon 97420, USA.


Animal cell cytokinesis results from patterned activation of the small GTPase Rho, which directs assembly of actomyosin in the equatorial cortex. Cytokinesis is restricted to a portion of the cell cycle following anaphase onset in which the cortex is responsive to signals from the spindle. We show that shortly after anaphase onset oocytes and embryonic cells of frogs and echinoderms exhibit cortical waves of Rho activity and F-actin polymerization. The waves are modulated by cyclin-dependent kinase 1 (Cdk1) activity and require the Rho GEF (guanine nucleotide exchange factor), Ect2. Surprisingly, during wave propagation, although Rho activity elicits F-actin assembly, F-actin subsequently inactivates Rho. Experimental and modelling results show that waves represent excitable dynamics of a reaction-diffusion system with Rho as the activator and F-actin the inhibitor. We propose that cortical excitability explains fundamental features of cytokinesis including its cell cycle regulation.

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