Cell polarity and adherens junction formation inhibit epithelial Fas cell death receptor signaling

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Finely tuned regulation of epithelial cell death maintains tissue integrity and homeostasis. At the cellular level, life and death decisions are controlled by environmental stimuli such as the activation of death receptors. We show that cell polarity and adherens junction formation prevent proapoptotic signals emanating from the Fas death receptor. Fas is sequestered in E-cadherin actin-based adhesion structures that are less able to induce downstream apoptosis signaling. Using a proteomic-based approach, we find that the polarity molecule Dlg1 interacts with the C-terminal PDZ-binding site in Fas and that this interaction decreases formation of the death-inducing complex upon engagement with Fas ligand (FasL), thus acting as an additional cell death protection mechanism. We propose that E-cadherin and Dlg1 inhibit FasL-induced cell death by two complementary but partially independent mechanisms that help to maintain epithelial homeostasis by protecting normal polarized epithelia from apoptosis. When polarity is lost, the Fas–cadherin–Dlg1 antiapoptotic complex is disrupted, and FasL can promote the elimination of compromised nonpolarized cells.
Funding Information
  • Inserm
  • Centre National de la Recherche Scientifique
  • Association pour la Recherche sur le Cancer
  • Labex Signalife (ANR-11-LABX-0028-01)
  • Centre National de la Recherche Scientifique
  • La Ligue Nationale Contre le Cancer
  • Ruban Rose Award
  • Institut Universitaire de France
  • Aix Marseille Université
  • Infrastructures Biologie Santé et Agronomie
  • Canceropôle PACA
  • Provence-Alpes-Côte d'Azur region
  • Institut Paoli-Calmettes
  • Centre de Recherche en Cancérologie de Marseille

This publication has 42 references indexed in Scilit: