Journal
TRENDS IN CELL BIOLOGY
Volume 31, Issue 6, Pages 500-513Publisher
CELL PRESS
DOI: 10.1016/j.tcb.2021.03.004
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Funding
- Flemish grants [Excellence of Science (EOS) MODEL-IDI, Fonds Wetenschappelijk Onderzoek (FWO)] [30826052]
- FWO [G.0E04.16N, G.0C76.18N, G.0B71.18N, G.0B96.20N, G035117N, 3G0H5517, 3G044718, 3G044818, 1.5.091.18N, S008419N]
- interuniversitair Bijzonder Onderzoeksfonds ATLANTIS [BOF20/IBF/039]
- Methusalem [BOF16/MET_V/007]
- Foundation against Cancer [FAF-F/2016/865, FAF-F/2020/1505]
- Cancer Research Institute Ghent (CRIG)
- Ghent Gut Inflammation Group (GIGG) consortia
- Vlaams Instituut voor Biotechnologie (VIB)
- University of Antwerp (Bijzonder Onderzoeksfonds/Methusalem grant) [42/FA020000/FFB190208]
- Fund for Scientific Research-Flanders (Odysseus) [G.0C49.13N]
- Ghent University [BOF24Y2019003201]
- Cure-AID Grant from the EU European Research Area Network for Research Programs on Rare Diseases
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The GSDM family consists of six gene clusters with a unique N-terminal domain, capable of executing plasma membrane permeabilization. The activity of GSDME and GSDMD, the most widely expressed and best-studied GSDMs, is directly regulated by protease-and kinase-dependent mechanisms. Evolutionary forces and a unique position of the PJVK gene are associated with complex inner-ear development in vertebrates.
The gasdermin (GSDM) family has evolved as six gene clusters (GSDMA-E and Pejvakin, PJVK), and GSDM proteins are characterized by a unique N-terminal domain (N-GSDM). With the exception of PJVK, the N-GSDM domain is capable of executing plasma membrane permeabilization. Depending on the cell death modality, several protease-and kinase-dependent mechanisms directly regulate the activity of GSDME and GSDMD, the two most widely expressed and best-studied GSDMs. We provide an overview of all GSDMs in terms of biological function, tissue expression, activation, regulation, and structure. In-depth phylogenetic analysis reveals that GSDM genes show many gene duplications and deletions, suggesting that strong evolutionary forces and a unique position of the PJVK gene are associated with the occurrence of complex inner-ear development in vertebrates.
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