ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation.
Science
; 362(6417): 956-960, 2018 11 23.
Article
em En
| MEDLINE
| ID: mdl-30467171
ABSTRACT
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Membrana Celular
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Cálcio
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Caspases
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Sinalização do Cálcio
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Complexos Endossomais de Distribuição Requeridos para Transporte
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Piroptose
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Proteínas de Neoplasias
Limite:
Animals
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Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Suíça