ArticleProceedings of the National Academy of Sciences of the United States of America2016
GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 574 papers, 1 of them a synthesis that pooled it.
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Who cites it
574 citing papers in PubMed, 1 synthesis or guideline pooled it, 881 citations in OpenAlex.
- Bibliometric analysis and mini-review of global research on pyroptosis in the field of cancer.Apoptosis : an international journal on programmed cell death · 2023Pooled it
- Novel model of pyroptosis-related molecular signatures for prognosis prediction of clear cell renal cell carcinoma patients.International journal of medical sciences · 2024Trial
- Unmasking programmed cell death in rhinovirus-driven asthma pathology.Biochemical Society transactions · 2026Review
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Innate immune sensors of inflammasomes and PANoptosomes: structural-mechanistic insights and therapeutic implications.Cell research · 2026Review
- Igniting antitumour immunity with cancer cell pyroptosis.Nature reviews. Cancer · 2026Review
- Pyroptosis in Patients with Ovarian Dysfunction and Infertility: Molecular Mechanisms and Therapeutics.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Intracellular lipopolysaccharide binds RETREG1/FAM134B to regulate ER remodeling upon bacterial infection.Autophagy · 2026Article
- Mechanisms and therapeutic strategies of pyroptosis in sepsis‑induced acute lung injury (Review).International journal of molecular medicine · 2026Review
- Mechanism and plasticity of primitive pyroptosis.Science advances · 2026Article
- A potassium-based single-atom catalyst enables acute lung injury immunotherapy in mice by inhibiting macrophage pyroptosis.Nature communications · 2026Article
- Theme and variations: activation and regulation of gasdermin-mediated inflammation.Biochemical Society transactions · 2026Review
- Pyroptosis: Molecular mechanisms and function.Journal of physiology and biochemistry · 2026Review
- Direct visualization of native GSDMD pores reveals lipid-driven stabilization during pyroptosis.Science advances · 2026Article
- The ALS- and FTD-associated proteins annexin A11 and CHMP2B act sequentially in plasma membrane repair.Developmental cell · 2026Article
- Review
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Chemerin Promotes Oral Squamous Cell Carcinoma Progression via NLRP3-Mediated Pyroptosis and the GSDMD-N Pathway.International dental journal · 2026Article
- Peptide binding at the gasdermin D exosite reveals the structural basis for targeting the site.Acta crystallographica. Section D, Structural biology · 2026Article
- Regulated Cell Death in Idiopathic Pulmonary Fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
514 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gasdermin-D (GsdmD) is a critical mediator of innate immune defense because its cleavage by the inflammatory caspases 1, 4, 5, and 11 yields an N-terminal p30 fragment that induces pyroptosis, a death program important for the elimination of intracellular bacteria. Precisely how GsdmD p30 triggers pyroptosis has not been established. Here we show that human GsdmD p30 forms functional pores within membranes. When liberated from the corresponding C-terminal GsdmD p20 fragment in the presence of liposomes, GsdmD p30 localized to the lipid bilayer, whereas p20 remained in the aqueous environment. Within liposomes, p30 existed as higher-order oligomers and formed ring-like structures that were visualized by negative stain electron microscopy. These structures appeared within minutes of GsdmD cleavage and released Ca(2+) from preloaded liposomes. Consistent with GsdmD p30 favoring association with membranes, p30 was only detected in the membrane-containing fraction of immortalized macrophages after caspase-11 activation by lipopolysaccharide. We found that the mouse I105N/human I104N mutation, which has been shown to prevent macrophage pyroptosis, attenuated both cell killing by p30 in a 293T transient overexpression system and membrane permeabilization in vitro, suggesting that the mutants are actually hypomorphs, but must be above certain concentration to exhibit activity. Collectively, our data suggest that GsdmD p30 kills cells by forming pores that compromise the integrity of the cell membrane.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.