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

doi:10.1038/s41419-022-04896-5

IOCAS-IR > 实验海洋生物学重点实验室

	GSDMEa-mediated pyroptosis is bi-directionally regulated by caspase and required for effective bacterial clearance in teleost
	Xu, Hang 1,2,3,4,5; Jiang, Shuai 1,2,3,4,5; Yu, Chao1,2,3,4,5 ; Yuan, Zihao 1,2,3,4; Sun, Li 1,2,3,4,5
	2022-05-24
发表期刊	CELL DEATH & DISEASE
ISSN	2041-4889
卷号	13 期号:5 页码:13
通讯作者	Jiang, Shuai(sjiang@gdio.ac.cn) ; Sun, Li(lsun@qdio.ac.cn)
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.
DOI	10.1038/s41419-022-04896-5
收录类别	SCI
语种	英语
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
WOS类目	Cell Biology
WOS记录号	WOS:000801162300003
出版者	SPRINGERNATURE
引用统计	被引频次：17[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/179390
专题	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, 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
第一作者单位	中国科学院海洋研究所; 中国科学院海洋大科学研究中心
通讯作者单位	中国科学院海洋研究所; 中国科学院海洋大科学研究中心
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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