Mechanisms of Gasdermin Family Members in Inflammasome Signaling and Cell Death

J Mol Biol. 2018 Sep 14;430(18 Pt B):3068-3080. doi: 10.1016/j.jmb.2018.07.002. Epub 2018 Jul 7.


The Gasdermin (GSDM) family consists of Gasdermin A (GSDMA), Gasdermin B (GSDMB), Gasdermin C (GSDMC), Gasdermin D (GSDMD), Gasdermin E (GSDME) and Pejvakin (PJVK). GSDMD is activated by inflammasome-associated inflammatory caspases. Cleavage of GSDMD by human or mouse caspase-1, human caspase-4, human caspase-5, and mouse caspase-11 liberates the N-terminal effector domain from the C-terminal inhibitory domain. The N-terminal domain oligomerizes in the cell membrane and forms a pore of 10-16 nm in diameter, through which substrates of a smaller diameter, such as interleukin-1β and interleukin-18, are secreted. The increasing abundance of membrane pores ultimately leads to membrane rupture and pyroptosis, releasing the entire cellular content. Other than GSDMD, the N-terminal domain of all GSDMs, with the exception of PJVK, have the ability to form pores. There is evidence to suggest that GSDMB and GSDME are cleaved by apoptotic caspases. Here, we review the mechanistic functions of GSDM proteins with respect to their expression and signaling profile in the cell, with more focused discussions on inflammasome activation and cell death.

Keywords: Caspase-1; Caspase-11; Inflammasomes; Innate immunity; Pyroptosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Biomarkers
  • Cell Death / genetics
  • Gene Expression Regulation
  • Humans
  • Immune System / immunology
  • Immune System / metabolism
  • Inflammasomes / metabolism*
  • Multigene Family*
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism*
  • Receptors, Pattern Recognition / metabolism
  • Signal Transduction*


  • Biomarkers
  • GSDMA protein, human
  • Inflammasomes
  • Neoplasm Proteins
  • Receptors, Pattern Recognition