title: A complex of p190RhoGAP-A and anillin modulates RhoA-GTP and the cytokinetic furrow in human cells.
abstract: The cytokinetic furrow is organized by the RhoA GTPase, which recruits actin and myosin II to the furrow and drives contractility. Here, we show that the RhoA GTPase-activting protein (GAP) p190RhoGAP-A (also known as ARHGAP35) has a role in cytokinesis and is involved in regulating levels of RhoA-GTP and contractility. Cells depleted of p190RhoGAP-A accumulate high levels of RhoA-GTP and markers of high RhoA activity in the furrow, resulting in failure of the cytokinetic furrow to progress to abscission. The loss of p190RhoGAP-A can be rescued by a low dose of the myosin II inhibitor blebbistatin, suggesting that cells fail cytokinesis because they have too much myosin activity. p190RhoGAP-A binds the cytokinetic organizer anillin, and mutants of p190RhoGAP-A that are unable to bind anillin or unable to inactivate RhoA fail to rescue cytokinesis defects in p190RhoGAP-A-depleted cells. Taken together, these data demonstrate that a complex of p190RhoGAP-A and anillin modulates RhoA-GTP levels in the cytokinetic furrow to ensure progression of cytokinesis.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, PO Box 800733, Charlottesville, VA 22908, USA Cancer Center, University of Virginia School of Medicine, PO Box 800733, Charlottesville, VA 22908, USA.
authors.forename: Arkadi
authors.initials: A
authors.lastname: Manukyan
authors.affiliation: Cancer Center, University of Virginia School of Medicine, PO Box 800733, Charlottesville, VA 22908, USA Department of Psychiatry and Behavioral Sciences and Jonsson Cancer Center, UCLA, Los Angeles, CA 90095-6900, USA Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, PO Box 800733, Charlottesville, VA 22908, USA.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Ludwig
authors.affiliation: Cancer Center, University of Virginia School of Medicine, PO Box 800733, Charlottesville, VA 22908, USA Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, PO Box 800733, Charlottesville, VA 22908, USA Beckman Corporation, Los Angeles, CA 90025, USA.
authors.forename: Sergio
authors.initials: S
authors.lastname: Sanchez-Manchinelly
authors.affiliation: Cancer Center, University of Virginia School of Medicine, PO Box 800733, Charlottesville, VA 22908, USA Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, PO Box 800733, Charlottesville, VA 22908, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Parsons
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, PO Box 800733, Charlottesville, VA 22908, USA Cancer Center, University of Virginia School of Medicine, PO Box 800733, Charlottesville, VA 22908, USA pts7h@virginia.edu.
authors.forename: P Todd
authors.initials: PT
authors.lastname: Stukenberg
mesh_terms: D048749:Cytokinesis / Q000187:drug effects / Q000502:physiology*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006576:Heterocyclic Compounds, 4 or More Rings; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C000591059:ANLN protein, human; C074560:ARHGAP35 protein, human; D020662:Guanine Nucleotide Exchange Factors; D006576:Heterocyclic Compounds, 4 or More Rings; D008840:Microfilament Proteins; D012097:Repressor Proteins; C066737:RHOA protein, human; C472645:blebbistatin; D020742:rhoA GTP-Binding Protein
keywords: Anillin; Cytokinesis; Myosin II; Rho; p190RhoGAP