title: Modeling the roles of protein kinase Cβ and η in single-cell wound repair.
abstract: Wounded cells such as Xenopus oocytes respond to damage by assembly and closure of an array of actin filaments and myosin-2 controlled by Rho GTPases, including Rho and Cdc42. Rho and Cdc42 are patterned around wounds in a characteristic manner, with active Rho concentrating in a ring-like zone inside a larger, ring-like zone of active Cdc42. How this patterning is achieved is unknown, but Rho and Cdc42 at wounds are subject to regulation by other proteins, including the protein kinases C. Specifically, Cdc42 and Rho activity are enhanced by PKCβ and inhibited by PKCη. We adapt a mathematical model of Simon and coworkers to probe the possible roles of these kinases. We show that PKCβ likely affects the magnitude of positive Rho-Abr feedback, whereas PKCη acts on Cdc42 inactivation. The model explains both qualitative and some overall quantitative features of PKC-Rho GTPase regulation. It also accounts for the previous, peculiar observation that ∼ 20% of cells overexpressing PKCη display zone inversions--that is, displacement of active Rho to the outside of the active Cdc42.
authors: Department of Mathematics and Statistics, University of Melbourne, Melbourne, VIC 3010, Australia.
authors: William R
authors: WR
authors: Holmes
authors: Department of Biomedical Physics, Ryerson University, Toronto, ON M5B 2K3, Canada.
authors: Laura
authors: L
authors: Liao
authors: Department of Zoology, Laboratory of Cell and Molecular Biology, University of Wisconsin, Madison, WI 53706.
authors: William
authors: W
authors: Bement
authors: Department of Mathematics, University of British Columbia, Vancouver, BC V6T 1Z2, Canada keshet@math.ubc.ca.
authors: Leah
authors: L
authors: Edelstein-Keshet
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D008954:Models, Biological; D009865:Oocytes / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta / Q000378:metabolism*; D059010:Single-Cell Analysis; D014945:Wound Healing / Q000502:physiology*; D014982:Xenopus laevis; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; C061570:protein kinase N; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D020741:rho GTP-Binding Proteins