ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation.

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State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_EC1D001C7201
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation.
Journal
Science
Author(s)
Rühl S., Shkarina K., Demarco B., Heilig R., Santos J.C., Broz P.
ISSN
1095-9203 (Electronic)
ISSN-L
0036-8075
Publication state
Published
Issued date
23/11/2018
Peer-reviewed
Oui
Volume
362
Number
6417
Pages
956-960
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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-1β 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.
Keywords
Aniline Compounds/metabolism, Animals, Apoptosis Regulatory Proteins/genetics, Apoptosis Regulatory Proteins/metabolism, Calcium/metabolism, Calcium Signaling, Caspase 1/metabolism, Caspases/genetics, Caspases/metabolism, Cell Membrane/metabolism, Cell Survival, Cells, Cultured, Endosomal Sorting Complexes Required for Transport/metabolism, Fluorescent Dyes/metabolism, HEK293 Cells, Humans, Inflammation/metabolism, Inflammation/pathology, Interleukin-1beta/metabolism, Macrophages, Mice, Neoplasm Proteins/genetics, Neoplasm Proteins/metabolism, Pyroptosis, Xanthenes/metabolism
Pubmed
Web of science
Create date
26/11/2018 9:11
Last modification date
20/08/2019 17:14
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