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

• DOI: 10.1083/jcb.201805071
• Publication Date: 2018-09-21T14:22:58Z
• Authors: Laurent Gagnoux-P...; Hala Awina; Stéphane Audebert; Aurélie Rossin; Magali Mondin; Franck Borgese; Carlota Planas-Botey; Amel Mettouchi; Jean-Paul Borg; Anne-Odile Hueber
• Keywords: Adherens junction; Fas ligand; PDZ domain; Cell polarity

Finely tuned regulation of epithelial cell death maintains tissue integrity and homeostasis. At the cellular level, life decisions are controlled by environmental stimuli such as activation receptors. We show that polarity adherens junction formation prevent proapoptotic signals emanating from Fas receptor. is sequestered in E-cadherin actin-based adhesion structures less able to induce downstream apoptosis signaling. Using a proteomic-based approach, we find molecule Dlg1 interacts with C-terminal PDZ-binding site this interaction decreases death-inducing complex upon engagement ligand (FasL), thus acting an additional protection mechanism. propose inhibit FasL-induced two complementary but partially independent mechanisms help maintain homeostasis protecting normal polarized epithelia apoptosis. When lost, Fas–cadherin–Dlg1 antiapoptotic disrupted, FasL can promote elimination compromised nonpolarized cells.