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IRF6 Regulates the Delivery of E-Cadherin to the Plasma Membrane

  • Angelo Antiguas
    Affiliations
    Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA
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  • Kris A. DeMali
    Affiliations
    Department of Biochemistry and Molecular Biology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA

    Department of Dermatology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA
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  • Martine Dunnwald
    Correspondence
    Correspondence: Martine Dunnwald, Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, 1-532 Bowen Science Building, 51 Newton Road, Iowa City, Iowa 52242, USA.
    Affiliations
    Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA
    Search for articles by this author
      IRF6 is a transcription factor that is required for craniofacial development and epidermal morphogenesis. Specifically, Irf6-deficient mice lack the terminally differentiated epidermal layers, leading to an absence of barrier function. This phenotype also includes intraoral adhesions due to the absence of the oral periderm, leading to the mislocalization of E-cadherin and other cell‒cell adhesion proteins of the oral epithelium. However, the mechanisms by which IRF6 controls the localization of cell adhesion proteins are not understood. In this study, we show that in human and murine keratinocytes, loss of IRF6 leads to a breakdown of epidermal sheets after mechanical stress. This defect is due to a reduction of adhesion proteins at the plasma membrane. Dynamin inhibitors rescued the IRF6-dependent resistance of epidermal sheets to mechanical stress, but only inhibition of clathrin-mediated endocytosis rescued the localization of junctional proteins at the membrane. Our data show that E-cadherin recycling but not its endocytosis is affected by loss of IRF6. Overall, we demonstrate a role for IRF6 in the delivery of adhesion proteins to the cell membrane.

      Abbreviations:

      AJ (adherens junction), HFK (human foreskin keratinocyte), KC (keratinocyte), sh (short hairpin), WT (wild type)
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