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Punching Holes in Cellular Membranes: Biology and Evolution of Gasdermins
Open accessAbstract
The gasdermin (GSDM) family has evolved as six gene clusters (GSDMA-E and Pejvakin, PJVK), and GSDM proteins are characterized by a unique N-terminal domain (N-GSDM). With the exception of PJVK, the N-GSDM domain is capable of executing plasma membrane permeabilization. Depending on the cell death modality, several protease- and kinase-dependent mechanisms directly regulate the activity of GSDME and GSDMD, the two most widely expressed and best-studied GSDMs. We provide an overview of all GSDMs in terms of biological function, tissue expression, activation, regulation, and structure. In-depth phylogenetic analysis reveals that GSDM genes show many gene duplications and deletions, suggesting that strong evolutionary forces and a unique position of the PJVK gene are associated with the occurrence of complex inner-ear development in vertebrates.
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“The structures enriched in the gasdermin Pfam annotation adopted a similar conformation to that of the mammalian gasdermin N terminus, especially of gasdermin E, which is considered to be evolutionary ancient34.”
From Clustering predicted structures at the scale of the known protein universe (2023) · cites this paper as [34]
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Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling
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Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores
Liu, X., Zhang, Z., Ruan, J., Pan, Y., Magupalli, V. G., Wu, H., & Lieberman, J. (2016) · Nature · doi:10.1038/nature18629 · Cited by 3,202
Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin
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Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion
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Metadata
- Authors
- De Schutter, E., Roelandt, R., Riquet, F. B., Van Camp, G., Wullaert, A., & Vandenabeele, P.
- Affiliations
- Vlaams Instituut voor Biotechnologie (BE)
- Université de Lille (FR)
- Corresponding author
- Vandenabeele, Peter
- Venue
- Trends in Cell Biology
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 31
- Issue
- 6
- Pages
- 500-513
- ISSN
- 0962-8924 (ISSN-L)
- OpenAlex
- W3139151250
- Cited by
- 158
- References
- 84
- Citations by year
- 2026: 17 · 2025: 24 · 2024: 35 · 2023: 34 · 2022: 36 · 2021: 10
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Trends in Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- LillOA (Université de Lille (University Of Lille)) (submittedVersion, other-oa)
- Funders
- Fonds Wetenschappelijk Onderzoek (FAF-F/2020/1505, 30826052, BOF20/IBF/039, BOF16/MET_V/007)
- Universiteit Gent (BOF24Y2019003201)
- Vlaams Instituut voor Biotechnologie
- Universiteit Antwerpen (42/FA020000/FFB190208)
- Stichting Tegen Kanker (FAF-F/2016/865)
- Fonds De La Recherche Scientifique - FNRS (3G044718, 3G044818, 1.5.091.18N, S008419N, 3G0H5517)
- European Commission
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- gasdermin, gasdermin D, gasdermin E, plasma membrane permeabilization, N-terminal domain, cell death, gene family evolution, gene duplication, gene deletion, phylogenetic analysis, inner ear development, protease regulation, kinase regulation, protein structure
- MeSH terms
- Animals, Biology, Cell Membrane, Neoplasm Proteins, Phylogeny, Cell Death
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