Epidermal loss of Gαq confers a migratory and differentiation defect in keratinocytes

Colleen L. Doçi, Constantinos M. Mikelis, Juan Luis Callejas-Valera, Karina K. Hansen, Alfredo A. Molinolo, Asuka Inoue, Stefan Offermanns, J. Silvio Gutkind

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4 Citations (Scopus)

Abstract

G-protein oupled receptors (GPCRs), which activate heterotrimeric G proteins, are an essential class of transmembrane receptors that are responsible for a myriad of signaling events in normal and pathologic conditions. Two members of the G protein family, Gαq and Gα11, activate one of the main GPCR pathways and function as oncogenes by integrating mitogen-stimulated signaling cascades that are active under malignant conditions. Recently, it has been shown that targeted deletion of Gα11 and Gαq from endothelial cells impairs the Rho-mediated formation of focal adherens junctions, suggesting that Gα11/q signaling may also play a significant role in cytoskeletal-mediated cellular responses in epithelial cells. Indeed, combined deletion of Gα11 and Gαq confers a significant migratory defect in keratinocytes that delays cutaneous wound healing in an in vivo setting. This delay can be attributed to a defect during the reepithelialization phase due to significantly attenuated migratory capacity of Gαq-null keratinocytes under combined Gα11 deficiency. In fact, cells lacking Gα11/q demonstrate a severely reduced ability to respond to mitogenic and migratory signals in the microenvironment, leading to inappropriate and premature terminal differentiation. These results suggest that Gα11/q signaling pathways may be critical for integrating mitogenic signals and cytoskeletal function to achieve normal physiological responses. Emergence of a malignant phenotype may therefore arise from both under- and overexpression of Gα11/q signaling, implicating its upstream regulation as a potential therapeutic target in a host of pathologic conditions.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Original languageEnglish
Article numbere0173692
JournalPloS one
Volume12
Issue number3
DOIs
Publication statusPublished - 2017 Mar

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Doçi, C. L., Mikelis, C. M., Callejas-Valera, J. L., Hansen, K. K., Molinolo, A. A., Inoue, A., Offermanns, S., & Gutkind, J. S. (2017). Epidermal loss of Gαq confers a migratory and differentiation defect in keratinocytes. PloS one, 12(3), [e0173692]. https://doi.org/10.1371/journal.pone.0173692