Abstract

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.

Keywords

InflammationProgrammed cell deathCell biologyComputational biologyBiologyImmunologyGeneticsApoptosis

MeSH Terms

Cell DeathCell MembraneCell Membrane PermeabilityHumansInflammationNeoplasm ProteinsPyroptosis

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Publication Info

Year
2019
Type
review
Volume
20
Issue
3
Pages
143-157
Citations
1460
Access
Closed

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Cite This

Petr Brož, Pablo Pelegrı́n, Feng Shao (2019). The gasdermins, a protein family executing cell death and inflammation. Nature reviews. Immunology , 20 (3) , 143-157. https://doi.org/10.1038/s41577-019-0228-2

Identifiers

DOI
10.1038/s41577-019-0228-2
PMID
31690840

Data Quality

Data completeness: 86%