title: MgcRacGAP restricts active RhoA at the cytokinetic furrow and both RhoA and Rac1 at cell-cell junctions in epithelial cells.
abstract: Localized activation of Rho GTPases is essential for multiple cellular functions, including cytokinesis and formation and maintenance of cell-cell junctions. Although MgcRacGAP (Mgc) is required for spatially confined RhoA-GTP at the equatorial cortex of dividing cells, both the target specificity of Mgc's GAP activity and the involvement of phosphorylation of Mgc at Ser-386 are controversial. In addition, Mgc's function at cell-cell junctions remains unclear. Here, using gastrula-stage Xenopus laevis embryos as a model system, we examine Mgc's role in regulating localized RhoA-GTP and Rac1-GTP in the intact vertebrate epithelium. We show that Mgc's GAP activity spatially restricts accumulation of both RhoA-GTP and Rac1-GTP in epithelial cells--RhoA at the cleavage furrow and RhoA and Rac1 at cell-cell junctions. Phosphorylation at Ser-386 does not switch the specificity of Mgc's GAP activity and is not required for successful cytokinesis. Furthermore, Mgc regulates adherens junction but not tight junction structure, and the ability to regulate adherens junctions is dependent on GAP activity and signaling via the RhoA pathway. Together these results indicate that Mgc's GAP activity down-regulates the active populations of RhoA and Rac1 at localized regions of epithelial cells and is necessary for successful cytokinesis and cell-cell junction structure.
authors.affiliation: Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Elaina B
authors.initials: EB
authors.lastname: Breznau
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Ansley C
authors.initials: AC
authors.lastname: Semack
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Tomohito
authors.initials: T
authors.lastname: Higashi
authors.affiliation: Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI 48109 Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109 annlm@umich.edu.
authors.forename: Ann L
authors.initials: AL
authors.lastname: Miller
mesh_terms: D000818:Animals; D048749:Cytokinesis / Q000502:physiology; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D023421:Models, Animal; D010766:Phosphorylation; D014982:Xenopus laevis; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; C115995:mgcRacGAP; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein