Teleost GSDMEc regulates GSDMEa-mediated pyroptosis

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Gasdermin (GSDM) is a family of proteins that execute pyroptosis after being activated by caspase (CASP) cleavage. Mammals possess five GSDM members (A - E) with pyroptotic ability. Teleosts only one GSDM, GSDME, exists in three orthologs, GSDMEa, b, and c. GSDMEa GSDMEb are known to induce pyroptosis, but the function GSDMEc unknown. The present study aimed elucidate teleost examine interplay among GSDME orthologs using snakehead Channa argus as representative species. Pyroptosis was assessed via microscopy biochemical assays. cleavage, oligomerization, membrane translocation were examined immunoblotting. interactions products confocal co-immunoprecipitation. knockdown fish vivo bacterial infection performed. C. possessed variants (CaGSDMEa, CaGSDMEc1, CaGSDMEc2). CaGSDMEa cleaved CASP (CaCASP) 1/8 produce an N-terminal fragment (NT), NT261, induced pyroptosis. CaGSDMEc1 CaGSDMEc2 also CaCASP1/8, resulting NTs, NT123 NT108, respectively, unable However, both NT108 could bind promote activity NT261 facilitating oligomerization translocation. interaction between NT123/NT108 depended on positively charged motif conserved metazoan essential localization NT261. Bacterial CaGSDMEa/CaCASP8 activation CaGSDMEc1/c2 cleavage cells, IL-1β/18 maturation extracellular DNA-net formation. CaGSDMEa/c1 significantly increased dissemination tissues reduced survival. Our results revealed functions interactive mechanism provided new insights into regulation lower vertebrates.

Язык: Английский

Controlling pyroptosis through post-translational modifications of gasdermin D

Developmental Cell, Год журнала: 2025, Номер 60(7), С. 994 - 1007

Опубликована: Апрель 1, 2025

Язык: Английский

Gasdermins in pyroptosis, inflammation, and cancer

Trends in Molecular Medicine, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский