Modeling the roles of protein kinase C? and ? 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 PKC? and inhibited by PKC?. We adapt a mathematical model of Simon and coworkers to probe the possible roles of these kinases. We show that PKC? likely affects the magnitude of positive Rho-Abr feedback, whereas PKC? 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 PKC? display zone inversions--that is, displacement of active Rho to the outside of the active Cdc42.

SUBMITTER: Holmes WR 

PROVIDER: S-EPMC4710240 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature