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ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation.
Rühl, Sebastian; Shkarina, Kateryna; Demarco, Benjamin; Heilig, Rosalie; Santos, José Carlos; Broz, Petr.
Afiliación
  • Rühl S; Focal Area Infection Biology, Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
  • Shkarina K; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Demarco B; Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
  • Heilig R; Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
  • Santos JC; Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
  • Broz P; Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
Science ; 362(6417): 956-960, 2018 11 23.
Article en En | MEDLINE | ID: mdl-30467171
Pyroptosis is a lytic form of cell death that is induced by inflammatory caspases upon activation of the canonical or noncanonical inflammasome pathways. These caspases cleave gasdermin D (GSDMD) to generate an N-terminal GSDMD fragment, which executes pyroptosis by forming membrane pores. We found that calcium influx through GSDMD pores serves as a signal for cells to initiate membrane repair by recruiting the endosomal sorting complexes required for transport (ESCRT) machinery to damaged membrane areas, such as the plasma membrane. Inhibition of the ESCRT-III machinery strongly enhances pyroptosis and interleukin-1ß release in both human and murine cells after canonical or noncanonical inflammasome activation. These results not only attribute an anti-inflammatory role to membrane repair by the ESCRT-III system but also provide insight into general cellular survival mechanisms during pyroptosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Membrana Celular / Calcio / Caspasas / Señalización del Calcio / Complejos de Clasificación Endosomal Requeridos para el Transporte / Piroptosis / Proteínas de Neoplasias Límite: Animals / Humans Idioma: En Revista: Science Año: 2018 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Membrana Celular / Calcio / Caspasas / Señalización del Calcio / Complejos de Clasificación Endosomal Requeridos para el Transporte / Piroptosis / Proteínas de Neoplasias Límite: Animals / Humans Idioma: En Revista: Science Año: 2018 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos