Institutional Repository of Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences
| 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
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| 2022-05-24 | |
| Source Publication | CELL DEATH & DISEASE
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| ISSN | 2041-4889 |
| Volume | 13Issue:5Pages:13 |
| Corresponding Author | Jiang, Shuai(sjiang@gdio.ac.cn) ; Sun, Li(lsun@qdio.ac.cn) |
| Abstract | 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. |
| DOI | 10.1038/s41419-022-04896-5 |
| Indexed By | SCI |
| Language | 英语 |
| Funding Project | 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 Research Area | Cell Biology |
| WOS Subject | Cell Biology |
| WOS ID | WOS:000801162300003 |
| Publisher | SPRINGERNATURE |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.qdio.ac.cn/handle/337002/179390 |
| Collection | 实验海洋生物学重点实验室 |
| Corresponding Author | Jiang, Shuai; Sun, Li |
| Affiliation | 1.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 Affilication | Institute of Oceanology, Chinese Academy of Sciences; Center for Ocean Mega-Science, Chinese Academy of Sciences |
| Corresponding Author Affilication | Institute 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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| File Name/Size | DocType | Version | Access | License | ||
| s41419-022-04896-5.p（5211KB） | 期刊论文 | 出版稿 | 延迟开放 | CC BY-NC-SA | View 2023-7-1后可获取 | |
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