Characterization of GSDME in amphioxus provides insights into the functional evolution of GSDM-mediated pyroptosis.

Autor: Xinli Wang, Xuxia Wei, Yan Lu, Qinghuan Wang, Rong Fu, Yin Wang, Qin Wang, Xiangyan Wang, Shangwu Chen, Anlong Xu, Shaochun Yuan
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: PLoS Biology, Vol 21, Iss 5, p e3002062 (2023)
Druh dokumentu: article
ISSN: 1544-9173
1545-7885
DOI: 10.1371/journal.pbio.3002062
Popis: Members of the gasdermin (GSDM) family are pore-forming effectors that cause membrane permeabilization and pyroptosis, a lytic proinflammatory type of cell death. To reveal the functional evolution of GSDM-mediated pyroptosis at the transition from invertebrates to vertebrates, we conducted functional characterization of amphioxus GSDME (BbGSDME) and found that it can be cleaved by distinct caspase homologs, yielding the N253 and N304 termini with distinct functions. The N253 fragment binds to cell membrane, triggers pyroptosis, and inhibits bacterial growth, while the N304 performs negative regulation of N253-mediated cell death. Moreover, BbGSDME is associated with bacteria-induced tissue necrosis and transcriptionally regulated by BbIRF1/8 in amphioxus. Interestingly, several amino acids that are evolutionarily conserved were found to be important for the function of both BbGSDME and HsGSDME, shedding new lights on the functional regulation of GSDM-mediated inflammation.
Databáze: Directory of Open Access Journals
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