Cell polarity and adherens junction formation inhibit epithelial Fas cell death receptor signaling
| Autor: | Gagnoux-Palacios, Laurent, Awina, Hala, Audebert, Stéphane, Rossin, Aurélie, Mondin, Magali, Borgese, Franck, Planas-Botey, Carlota, Mettouchi, Amel, Borg, Jean-Paul, Hueber, Anne-Odile |
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| Přispěvatelé: | Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute of Developmental Biology and Cancer (IBDC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Toxines bactériennes - Bacterial Toxins, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), This work was supported by institutional funding from Inserm, Centre National de la Recherche Scientifique, and by grants from the Association pour la Recherche sur le Cancer and the LABEX SIGNALIFE program (ANR-11-LABX-0028-01). J.-P. Borg’s laboratory is supported by La Ligue Nationale Contre le Cancer (Label Ligue) and Ruban Rose Award. J.-P. Borg is a scholar of Institut Universitaire de France. Proteomic analyses were done using the mass spectrometry facility of Aix Marseille Université Proteomics labeled 'Plateforme technologique de l’Université Aix-Marseille,' supported by Infrastructures Biologie Santé et Agronomie, the Cancéropôle PACA, the Provence-Alpes-Côte d'Azur Region, the Institut Paoli-Calmettes, and the Centre de Recherche en Cancérologie de Marseille., ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), ANR: 11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Proteomics
Fas Ligand Protein MESH: Cell Line Tumor MESH: Adaptor Proteins Signal Transducing/metabolism [SDV]Life Sciences [q-bio] MESH: Epithelial Cells/cytology [SDV.BC]Life Sciences [q-bio]/Cellular Biology MESH: Cadherins/genetics MESH: fas Receptor/genetics Discs Large Homolog 1 Protein MESH: Membrane Proteins/genetics MESH: Adaptor Proteins Signal Transducing/genetics Protein Domains Antigens CD Cell Line Tumor Report MESH: Multiprotein Complexes/genetics Humans MESH: Membrane Proteins/metabolism fas Receptor MESH: Multiprotein Complexes/metabolism Research Articles MESH: fas Receptor/metabolism Adaptor Proteins Signal Transducing MESH: Humans MESH: Adherens Junctions/genetics MESH: Cadherins/metabolism MESH: Proteomics Cell Polarity Membrane Proteins Epithelial Cells Adherens Junctions Cadherins MESH: Fas Ligand Protein/genetics MESH: Fas Ligand Protein/metabolism MESH: Epithelial Cells/metabolism Multiprotein Complexes MESH: Antigens CD/genetics MESH: Protein Domains MESH: Cell Polarity |
| Zdroj: | Journal of Cell Biology Journal of Cell Biology, 2018, 217 (11), pp.3839-3852. ⟨10.1083/jcb.201805071⟩ The Journal of Cell Biology Journal of Cell Biology, Rockefeller University Press, 2018, 217 (11), pp.3839-3852. ⟨10.1083/jcb.201805071⟩ |
| ISSN: | 0021-9525 1540-8140 |
| Popis: | Control of epithelial cell death is crucial to maintaining tissue integrity. Gagnoux-Palacios et al. show that cell polarity and adherens junction formation prevent proapoptotic signals emanating from the Fas death receptor. Therefore, Fas-dependent cell death contributes to the elimination of nonpolarized or nonadherent cells from human epithelia. 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. |
| Databáze: | OpenAIRE |
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