Modeling the roles of protein kinase Cβ and η in single-cell wound repair.

Holmes WR, Liao L, Bement W, Edelstein-Keshet L
Mol Biol Cell. 2015 26 (22): 4100-8

PMID: 26310444 · PMCID: PMC4710240 · DOI:10.1091/mbc.E15-06-0383

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.

© 2015 Holmes, Liao, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

MeSH Terms (11)

Actin Cytoskeleton Actins Animals Models, Biological Oocytes Protein Kinase C Protein Kinase C beta rho GTP-Binding Proteins Single-Cell Analysis Wound Healing Xenopus laevis

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