Related Experiment Video
Updated: Jul 10, 2025
10:23
Evaluation of Caspase Activation to Assess Innate Immune Cell Death
Published on: January 20, 2023
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Caspase-1 activates gasdermin A in non-mammals
Zachary P Billman1,2,3,4, Stephen B Kovacs1,2,3,4, Bo Wei1,3
1Duke University School of Medicine.
Biorxiv : the Preprint Server for Biology
|November 21, 2023
Summary
Gasdermins trigger pyroptosis, a form of cell death. Caspase-1, a protease, evolved to cleave different gasdermins, including GSDMA in birds and GSDMD in mammals, revealing a shifting target specificity over time.
Area of Science:
- Immunology
- Evolutionary Biology
- Cell Biology
Background:
- Gasdermins are key mediators of pyroptosis, a regulated cell death pathway.
- Mammals possess five gasdermin proteins (GSDMA-E), activated by proteases like caspases.
- The activation mechanism for GSDMA remains largely unknown.
Conclusions:
- Caspase-1 has a long-standing but dynamic evolutionary association with gasdermins.
- Caspase-1's target gasdermin has shifted throughout vertebrate evolution, from GSDME in fish to GSDMA in amphibians/reptiles/birds, and GSDMD in mammals.
- Understanding these evolutionary shifts provides insight into the regulation of pyroptosis.
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