Gasdermins: Effectors of pyroptosis

By S. B. Kovacs, Edward A. Miao. Trends in Cell Biology, 2017

1,156 citations recorded by the source corpus.

Pyroptosis is a form of lytic programmed cell death initiated by inflammasomes, which detect cytosolic contamination or perturbation. This drives activation of caspase-1 or caspase-11/4/5, which cleave gasdermin D, separating its N-terminal pore-forming domain (PFD) from the C-terminal repressor domain (RD). The PFD oligomerizes to form large pores in the membrane that drive swelling and membrane rupture. Gasdermin D is one of six (in humans) gasdermin family members; several other gasdermins have also been shown to form pores that cause pyroptosis after cleavage to activate their PFDs. One of these, gasdermin E, is activated by caspase-3 cleavage. We review our current understanding of pyroptosis as well as current knowledge of the gasdermin family.

Subfields: Hematology, Molecular Biology, Parasitology

View Paper: https://www.semanticscholar.org/paper/f07de787a82335d26e7cda2aa16208b47105769a

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Hematology

1. T. Kanneganti
2. D. Tang

In Molecular Biology

1. D. Tang
2. Xin Chen
3. T. Kanneganti
4. D. Klionsky
5. R. Malireddi
6. S. Kesavardhana
7. P. Boya
8. Guido Kroemer

In Parasitology

1. D. Klionsky
2. D. Tang
3. N. Mizushima
4. Zhifen Yang

Citations in the corpus

• Lysosomal membrane permeabilization and cell death (2018, background): “helical structure that recruits caspase-1, leading to the maturation of IL-1β-family cytokines and gasdermin-D, and consequent release of cytokines into the extracellular space.(104,105) Cholesterol crystals, protein aggregates such as β-amyloid, and bacterial products disrupt lyso-”
• Pattern Recognition Receptors and the Host Cell Death Molecular Machinery (2018, background): “The N-terminal domain, also called Pore-Forming Domain (PFD) (149) oligomerizes and associates with lipids in the inner plasma membrane to form 10–33 nm pores leading to cell swelling and eventually to cell lysis (150– 153).”
• Role of pyroptosis in inflammation and cancer (2022, background): “Recent studies have concentrated on the regulatory mechanisms of tumor pyroptosis, finding that the pyroptosis pathway of tumor cells is completely different from that of macrophage pyroptosis, as evidenced by the finding that the nPD-L1-GSDMCcaspase-8 pathway mediates pyroptosis to lead to tumor de”
• Copper metabolism in cell death and autophagy (2023, background): “Pyroptosis is a form of lytic programmed cell death initiated by inflammasomes, which is driven by the activation of caspase family proteins, including classical CASP1 (caspase 1) and non-classical CASP4/CASP11 (caspase 4) or CASP5 (caspase 5) [115,116].”
• Caspases in Cell Death, Inflammation, and Gasdermin-Induced Pyroptosis (2020, background): “The gasdermin protein family consists of GSDMA, GSDMB, GSDMC, GSDMD, GSDME (DFNA5), and DFNB59 (75, 118, 119).”
• The pore forming protein gasdermin D regulates interleukin-1 secretion from living macrophages (2017, neutral): “We also examined the release of enzymatically active tetrameric LDH from the liposome lumen, which has a diameter of 10 nm (Kovacs and Miao, 2017).”