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GSDMEa-mediated pyroptosis is bi-directionally regulated by caspase and required for effective bacterial clearance in teleost
Xu, Hang1,2,3,4,5; Jiang, Shuai1,2,3,4,5; Yu, Chao1,2,3,4,5; Yuan, Zihao1,2,3,4; Sun, Li1,2,3,4,5
2022-05-24
Source PublicationCELL DEATH & DISEASE
ISSN2041-4889
Volume13Issue:5Pages:13
Corresponding AuthorJiang, Shuai(sjiang@gdio.ac.cn) ; Sun, Li(lsun@qdio.ac.cn)
AbstractGasdermin (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.
DOI10.1038/s41419-022-04896-5
Indexed BySCI
Language英语
Funding ProjectNational 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 Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000801162300003
PublisherSPRINGERNATURE
Citation statistics
Document Type期刊论文
Identifierhttp://ir.qdio.ac.cn/handle/337002/179390
Collection实验海洋生物学重点实验室
Corresponding AuthorJiang, Shuai; Sun, Li
Affiliation1.Chinese Acad Sci, Inst Oceanol, CAS, Qingdao, Peoples R China
2.Chinese Acad Sci, Inst Oceanol, Shandong Prov Key Lab Expt Marine Biol, Qingdao, Peoples R China
3.Chinese Acad Sci, CAS Ctr Ocean Megasci, Qingdao, Peoples R China
4.Pilot Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Qingdao, Peoples R China
5.Univ Chinese Acad Sci, Beijing, Peoples R China
First Author AffilicationInstitute of Oceanology, Chinese Academy of Sciences;  Center for Ocean Mega-Science, Chinese Academy of Sciences
Corresponding Author AffilicationInstitute of Oceanology, Chinese Academy of Sciences;  Center for Ocean Mega-Science, Chinese Academy of Sciences
Recommended Citation
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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