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Punching Holes in Cellular Membranes: Biology and Evolution of Gasdermins

期刊

TRENDS IN CELL BIOLOGY
卷 31, 期 6, 页码 500-513

出版社

CELL PRESS
DOI: 10.1016/j.tcb.2021.03.004

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资金

  1. Flemish grants [Excellence of Science (EOS) MODEL-IDI, Fonds Wetenschappelijk Onderzoek (FWO)] [30826052]
  2. FWO [G.0E04.16N, G.0C76.18N, G.0B71.18N, G.0B96.20N, G035117N, 3G0H5517, 3G044718, 3G044818, 1.5.091.18N, S008419N]
  3. interuniversitair Bijzonder Onderzoeksfonds ATLANTIS [BOF20/IBF/039]
  4. Methusalem [BOF16/MET_V/007]
  5. Foundation against Cancer [FAF-F/2016/865, FAF-F/2020/1505]
  6. Cancer Research Institute Ghent (CRIG)
  7. Ghent Gut Inflammation Group (GIGG) consortia
  8. Vlaams Instituut voor Biotechnologie (VIB)
  9. University of Antwerp (Bijzonder Onderzoeksfonds/Methusalem grant) [42/FA020000/FFB190208]
  10. Fund for Scientific Research-Flanders (Odysseus) [G.0C49.13N]
  11. Ghent University [BOF24Y2019003201]
  12. Cure-AID Grant from the EU European Research Area Network for Research Programs on Rare Diseases

向作者/读者索取更多资源

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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