CD95 triggers Orai1-mediated localized Ca2+ entry, regulates recruitment of protein kinase C (PKC) β2, and prevents death-inducing signaling complex formation
| Autor: | Anne-Marie Vacher, Patrick Legembre, Bruno Ségui, Laurence Bresson-Bepoldin, Benjamin Chaigne-Delalande, Pierre Vacher, Thierry Levade, Thomas Ducret, Josy Reiffers, Jean-François Moreau, Nadine Khadra, Aubin Penna, Michael D. Cahalan |
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| Přispěvatelé: | Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140, Validation et identification de nouvelles cibles en oncologie (VINCO), Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié - CRLCC Bordeaux-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Bordeaux Segalen - Bordeaux 2, Department of Physiology and Biophysics and Center for Immunology, University of California [Irvine] (UCI), University of California-University of California, Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by Agence Nationale de la Recherche (ANR JC07_183182), Institut National du Cancer (Projets Libres Recherche Biomédicale), Cancéropole Grand Ouest, Région Bretagne, Rennes Métropole, Université de Rennes-1, Ligue Contre le Cancer (Comités d'Ille-et-Vilaine/du Morbihan/des Côtes d'Armor/du Maine et Loire/des Landes), and the National Institutes of Health (Grant NS-14609, to M.D.C.). N.K. is supported by Region Bretagne (Allocation de Recherche Doctorale)., Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2, Université de Rennes (UR), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), De Villemeur, Hervé |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Caspase complex
Protein Kinase C beta MESH: Flow Cytometry [SDV.BC]Life Sciences [q-bio]/Cellular Biology MESH: Caspase 8 03 medical and health sciences 0302 clinical medicine MESH: Microscopy Confocal MESH: Blotting Western FADD [SDV.BC] Life Sciences [q-bio]/Cellular Biology Protein kinase C 030304 developmental biology Death domain 0303 health sciences MESH: Statistics Nonparametric MESH: Caspase 10 Multidisciplinary MESH: Humans biology MESH: Immunoprecipitation MESH: Apoptosis STIM1 MESH: Multiprotein Complexes MESH: Fas-Associated Death Domain Protein MESH: Protein Kinase C MESH: Fas Ligand Protein Cell biology MESH: Antigens CD95 MESH: Cell Line 030220 oncology & carcinogenesis MESH: Calcium Death-inducing signaling complex biology.protein MESH: Calcium Channels Caspase 10 |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2011, 108 (47), pp.19072-7. ⟨10.1073/pnas.1116946108⟩ Proceedings of the National Academy of Sciences of the United States of America, 2011, 108 (47), pp.19072-7. ⟨10.1073/pnas.1116946108⟩ |
| ISSN: | 0027-8424 1091-6490 |
| DOI: | 10.1073/pnas.1116946108⟩ |
| Popis: | The death receptor CD95 plays a pivotal role in immune surveillance and immune tolerance. Binding of CD95L to CD95 leads to recruitment of the adaptor protein Fas-associated death domain protein (FADD), which in turn aggregates caspase-8 and caspase-10. Efficient formation of the CD95/FADD/caspase complex, known as the death-inducing signaling complex (DISC), culminates in the induction of apoptosis. We show that cells exposed to CD95L undergo a reorganization of the plasma membrane in which the Ca 2+ release-activated Ca 2+ channel Orai1 and the endoplasmic reticulum-resident activator stromal interaction molecule 1 colocalize with CD95 into a micrometer-sized cluster in which the channel elicits a polarized entry of calcium. Orai1 knockdown and expression of a dominant negative construct (Orai1E106A) reveal that on CD95 engagement, the Orai1-driven localized Ca 2+ influx is fundamental to recruiting the Ca 2+ -dependent protein kinase C (PKC) β2 to the DISC. PKCβ2 in turn transiently holds the complex in an inactive status, preventing caspase activation and transmission of the apoptotic signal. This study identifies a biological role of Ca 2+ and the Orai1 channel that drives a transient negative feedback loop, introducing a lag phase in the early steps of the CD95 signal. We suggest that these localized events provide a time of decision to prevent accidental cell death. |
| Databáze: | OpenAIRE |
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