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GSDMEa-mediated pyroptosis is bi-directionally regulated by caspase and required for effective bacterial clearance in teleost

文献类型：期刊论文

作者Xu, Hang1,2,3,4,5; Jiang, Shuai1,2,3,4,5; Yu, Chao1,2,3,4,5; Yuan, Zihao1,3,4,5; Sun, Li1,2,3,4,5
刊名CELL DEATH & DISEASE
出版日期2022-05-24
卷号13期号:5页码:13
ISSN号2041-4889
DOI10.1038/s41419-022-04896-5
通讯作者Jiang, Shuai(sjiang@gdio.ac.cn) ; Sun, Li(lsun@qdio.ac.cn)
英文摘要Gasdermin (GSDM) is a family of pore-forming proteins that, after cleavage by caspase (CASP), induce a type of programmed necrotic cell death called pyroptosis. Gasdermin E (GSDME) is the only pyroptosis-inducing member of the GSDM family existing in teleost. To date, the regulation and function of teleost GSDME in response to bacterial infection remain elusive. In this study, we observed activation of GSDME, as well as multiple CASPs, in turbot Scophthalmus maximus during the infection of the bacterial pathogen Vibrio harveyi. Turbot has two GSDME orthologs named SmGSDMEa and SmGSDMEb. We found that SmGSDMEa was specifically cleaved by turbot CASP (SmCASP) 3/7 and SmCASP6, which produced two different N-terminal (NT) fragments. Only the NT fragment produced by SmCASP3/7 cleavage was able to induce pyroptosis. Ectopically expressed SmCASP3/7 activated SmGSDMEa, resulting in pyroptotic cell death. In contrast, SmCASP6 inactivated SmGSDMEa by destructive cleavage of the NT domain, thus nullifying the activation effect of SmCASP3/7. Unlike SmGSDMEa, SmGSDMEb was cleaved by SmCASP8 and unable to induce cell death. V. harveyi infection dramatically promoted the production and activation of SmGSDMEa, but not SmGSDMEb, and caused pyroptosis in turbot. Interference with SmCASP3/7 activity significantly enhanced the invasiveness and lethality of V. harveyi in a turbot infection model. Together, these results revealed a previously unrecognized bi-directional regulation mode of GSDME-mediated pyroptosis, and a functional difference between teleost GSDMEa and GSDMEb in the immune defense against bacterial infection.
资助项目National Key Research and Development Project of China[2018YFD0900500] ; Youth Innovation Promotion Association CAS[2021204] ; Taishan Scholar Program of Shandong Province ; National Natural Science Foundation of China[41876175]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000801162300003
出版者SPRINGERNATURE
源URL[http://ir.qdio.ac.cn/handle/337002/179389]  
专题海洋研究所_实验海洋生物学重点实验室
通讯作者Jiang, Shuai; Sun, Li
作者单位1.Chinese Acad Sci, CAS Ctr Ocean Megasci, Qingdao, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Pilot Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Qingdao, Peoples R China
4.Chinese Acad Sci, Inst Oceanol, Shandong Prov Key Lab Expt Marine Biol, Qingdao, Peoples R China
5.Chinese Acad Sci, Inst Oceanol, CAS, Qingdao, Peoples R China
推荐引用方式
GB/T 7714		 Xu, Hang,Jiang, Shuai,Yu, Chao,et al. GSDMEa-mediated pyroptosis is bi-directionally regulated by caspase and required for effective bacterial clearance in teleost[J]. CELL DEATH & DISEASE,2022,13(5):13.
APA Xu, Hang,Jiang, Shuai,Yu, Chao,Yuan, Zihao,&Sun, Li.(2022).GSDMEa-mediated pyroptosis is bi-directionally regulated by caspase and required for effective bacterial clearance in teleost.CELL DEATH & DISEASE,13(5),13.
MLA Xu, Hang,et al."GSDMEa-mediated pyroptosis is bi-directionally regulated by caspase and required for effective bacterial clearance in teleost".CELL DEATH & DISEASE 13.5(2022):13.

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来源：海洋研究所

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