The gasdermins, a protein family executing cell death and inflammation
Open accessAbstract
The gasdermins are a family of recently identified pore-forming effector proteins that cause membrane permeabilization and pyroptosis, a lytic pro-inflammatory type of cell death. Gasdermins contain a cytotoxic N-terminal domain and a C-terminal repressor domain connected by a flexible linker. Proteolytic cleavage between these two domains releases the intramolecular inhibition on the cytotoxic domain, allowing it to insert into cell membranes and form large oligomeric pores, which disrupts ion homeostasis and induces cell death. Gasdermin-induced pyroptosis plays a prominent role in many hereditary diseases and (auto)inflammatory disorders as well as in cancer. In this Review, we discuss recent developments in gasdermin research with a focus on mechanisms that control gasdermin activation, pore formation and functional consequences of gasdermin-induced membrane permeabilization.
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GSDMD is the only gasdermin protein with a cleavage site for caspase-1.
“GSDMD is the only gasdermin protein with a cleavage site for caspase-1 [67].”
From Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer’s disease (2023) · cites this paper as [67]
The section on signaling pathways (p. 6) explicitly excepts a minor GSDMB splice variant from the statement that other gasdermins lack a caspase-1 cleavage site. The gasdermin family section (p. 4) further says that this GSDMB isoform has such a site and can be cleaved by caspase-1. GSDMD is therefore not the only gasdermin protein with one. (LLM, conf=0.90)
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- Authors
- Broz, P., Pelegrín, P., & Shao, F.
- Affiliations
- National Institute of Biological Sciences, Beijing (CN)
- Corresponding author
- Shao, Feng
- Venue
- Nature Reviews Immunology
- Published
- 2019-11-05
- Volume
- 20
- Issue
- 3
- Pages
- 143-157
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- OpenAlex
- W2983652778
- Cited by
- 1,641
- References
- 10
- Citations by year
- 2026: 218 · 2025: 286 · 2024: 292 · 2023: 280 · 2022: 305 · 2021: 186 · 2020: 73 · 2019: 1
- FWCI
- 12.63
- Type
- journal article
- Language
- en
- Open access
- green
- serval.unil.ch
- Licence
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- IRIS (submittedVersion)
- Funders
- National Science Foundation (81788101)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (20859, 175576)
- National Natural Science Foundation of China (81788101, 2016YFA0501500, 2017YFA0505900)
- Chinese Academy of Sciences (XDB08020202, 81788101)
- Sociedad Española de Reumatología
- Sociedad Española de Reumatología Pediátrica
- European Regional Development Fund (SAF2017-88276-R, SAF2017)
- H2020 European Research Council (770988)
- FP7 Ideas: European Research Council (614578)
- 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 › Immune Response and Inflammation
- Keywords
- gasdermin, pyroptosis, pore-forming proteins, membrane permeabilization, cell death, inflammation, proteolytic cleavage, repressor domain, autoinflammatory disease, cancer
- MeSH terms
- Pyroptosis, Cell Membrane, Cell Membrane Permeability, Humans, Inflammation, Neoplasm Proteins, Cell Death
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