title: Activator-inhibitor coupling between Rho signalling and actin assembly makes the cell cortex an excitable medium.
abstract: 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.
authors.affiliation: Laboratory of Cell and Molecular Biology, Graduate Program in Cell and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Bement
authors.affiliation: Centre for Synthetic and Systems Biology, University of Edinburgh, Edinburgh EH9 3BF, UK.
authors.forename: Marcin
authors.initials: M
authors.lastname: Leda
authors.affiliation: Laboratory of Cell and Molecular Biology, Graduate Program in Cell and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Moe
authors.affiliation: Laboratory of Cell and Molecular Biology, Graduate Program in Cell and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Kita
authors.affiliation: Laboratory of Cell and Molecular Biology, Graduate Program in Cell and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Larson
authors.affiliation: Laboratory of Cell and Molecular Biology, Graduate Program in Cell and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Adriana E
authors.initials: AE
authors.lastname: Golding
authors.affiliation: Laboratory of Cell and Molecular Biology, Graduate Program in Cell and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Pfeuti
authors.affiliation: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Boston, Massachusetts  02142, USA.
authors.forename: Kuan-Chung
authors.initials: KC
authors.lastname: Su
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48190, USA.
authors.forename: Ann L
authors.initials: AL
authors.lastname: Miller
authors.affiliation: Centre for Synthetic and Systems Biology, University of Edinburgh, Edinburgh EH9 3BF, UK.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Goryachev
authors.affiliation: Oregon Institute of Marine Biology, University of Oregon, Charleston, Oregon 97420, USA.
authors.forename: George
authors.initials: G
authors.lastname: von Dassow
mesh_terms: D000199:Actins / Q000378:metabolism*; D000705:Anaphase; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism; D048749:Cytokinesis; D003593:Cytoplasm / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D007700:Kinetics; D018613:Microscopy, Confocal; D008870:Microtubules / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D058105:Polymerization; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism; D013215:Starfish; D059008:Time-Lapse Imaging / Q000379:methods; D014982:Xenopus laevis; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D020662:Guanine Nucleotide Exchange Factors; D016203:CDC2 Protein Kinase; D020741:rho GTP-Binding Proteins