GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes
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Significance: Pyroptosis is a form of cell death that is critical for eliminating innate immune cells infected with intracellular bacteria. Microbial products such as lipopolysaccharide, which is a component of Gram-negative bacteria, trigger activation of the inflammatory caspases 1, 4, 5, and 11. These proteases cleave the cytoplasmic protein Gasdermin-D into two pieces, p20 and p30. The p30 fragment is cytotoxic when liberated from the p20 fragment. Our work suggests that p30 induces pyroptosis by associating with cell membranes and forming pores that perturb vital electrochemical gradients. The resulting imbalance causes the cell to lyse and release intracellular components that can alert other immune cells to the threat of infection.
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Membrane targeting enables GSDMD-N oligomerization, generating a pore responsible for rapid plasma membrane permeabilization.
“Membrane targeting enables GSDMD-N oligomerization, generating a pore that is responsible for rapid plasma membrane permeabilization [629–633].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [631]
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- Authors
- Aglietti, R. A., Estevez, A., Gupta, A., Ramirez, M. G., Liu, P. S., Kayagaki, N., Ciferri, C., Dixit, V. M., & Dueber, E. C.
- Affiliations
- Genentech (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-06-23
- Volume
- 113
- Issue
- 28
- Pages
- 7858-7863
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4948338
- OpenAlex
- W2461756806
- Cited by
- 898
- References
- 29
- Citations by year
- 2026: 48 · 2025: 84 · 2024: 98 · 2023: 110 · 2022: 132 · 2021: 98 · 2020: 88 · 2019: 85 · 2018: 78 · 2017: 58 · 2016: 16
- FWCI
- 41.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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 D, pyroptosis, caspase-11, pore formation, membrane permeabilization, liposomes, oligomerization, calcium release, macrophages, hypomorphic mutation, innate immunity
- MeSH terms
- Pyroptosis, Gasdermins, Animals, Humans, Liposomes, Mutation, Neoplasm Proteins, Caspases, Phosphate-Binding Proteins, Intracellular Signaling Peptides and Proteins, Mice, HEK293 Cells
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