Beyond inflammasomes: emerging function of gasdermins during apoptosis and NETosis
- 3 December 2019
- journal article
- review article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 39 (2), e103397
- https://doi.org/10.15252/embj.2019103397
Abstract
Programmed cell death is a key mechanism involved in several biological processes ranging from development and homeostasis to immunity, where it promotes the removal of stressed, damaged, malignant or infected cells. Abnormalities in the pathways leading to initiation of cell death or removal of dead cells are consequently associated with a range of human diseases including infections, autoinflammatory disease, neurodegenerative disease and cancer. Apoptosis, pyroptosis and NETosis are three well‐studied modes of cell death that were traditionally believed to be independent of one another, but emerging evidence indicates that there is extensive cross‐talk between them, and that all three pathways can converge onto the activation of the same cell death effector—the pore‐forming protein Gasdermin D (GSDMD). In this review, we highlight recent advances in gasdermin research, with a particular focus on the role of gasdermins in pyroptosis, NETosis and apoptosis, as well as cell type‐specific consequences of gasdermin activation. In addition, we discuss controversies surrounding a related gasdermin family protein, Gasdermin E (GSDME), in mediating pyroptosis and secondary necrosis following apoptosis, chemotherapy and inflammasome activation.Keywords
Funding Information
- H2020 Marie Skłodowska-Curie Actions (MSCA‐IF‐2018‐838252)
- H2020 European Research Council (ERC2017‐CoG‐770988)
This publication has 96 references indexed in Scilit:
- IAPs limit activation of RIP kinases by TNF receptor 1 during developmentThe EMBO Journal, 2012
- Inflammasome-dependent Pyroptosis and IL-18 Protect against Burkholderia pseudomallei Lung Infection while IL-1β Is DeleteriousPLoS Pathogens, 2011
- Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteriaNature Immunology, 2010
- Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular trapsThe Journal of cell biology, 2010
- In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 daysBlood, 2010
- Inflammatory arthritis in caspase 1 gene–deficient mice: Contribution of proteinase 3 to caspase 1–independent production of bioactive interleukin‐1βArthritis & Rheumatism, 2009
- Caspase 1–independent activation of interleukin‐1β in neutrophil‐predominant inflammationArthritis & Rheumatism, 2009
- TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivoGenes & Development, 2005
- Essential function for the kinase TAK1 in innate and adaptive immune responsesNature Immunology, 2005
- Embryonic Lethality, Liver Degeneration, and Impaired NF-κB Activation in IKK-β-Deficient MiceImmunity, 1999