Teleost Gasdermin E Is Cleaved by Caspase 1, 3, and 7 and Induces Pyroptosis

doi:10.4049/jimmunol.1900383

IOCAS-IR > 实验海洋生物学重点实验室

	Teleost Gasdermin E Is Cleaved by Caspase 1, 3, and 7 and Induces Pyroptosis
	Jiang, Shuai 1,2; Gu, Hanjie 1,2,3; Zhao, Yan1,2,3 ; Sun, Li 1,2
	2019-09-01
发表期刊	JOURNAL OF IMMUNOLOGY
ISSN	0022-1767
卷号	203 期号:5 页码:1369-1382
通讯作者	Sun, Li([email protected])
摘要	Pyroptosis is a newly defined gasdermin (GSDM)-dependent inflammatory type of programmed cell death. Different from mammals, which have a panel of pyroptotic GSDM members (e.g., GSDMA-E), teleosts possess only GSDME. The pyroptotic activity and regulation mechanism of teleost GSDME remain to be elucidated. In this work, we investigated the activity of the teleost Cynoglossus semilaevis (tongue sole) GSDME (CsGSDME) in association with different caspases (CASPs). We found that CsGSDME exerted pyroptotic and bactericidal activities through its N-terminal domain. Unlike human GSDME, which is exclusively cleaved by CASP3, CsGSDME was cleaved by C. semilaevis CASP (CsCASP) 1 with high efficiency and by CsCASP3 and 7 with comparatively low efficiencies, and all cleavages occurred at the 243FEVD246 site in the interdomain linker region of CsGSDME. Mutation of Phe(243) to Asp/Ala and Asp(246) to Ala in 243FEVD246 altered the cleavage preference of CsCASP1, 3, and 7. Treatment with loss-of-function CsCASP mutants or inhibition of CsCASP activity resulted in failure of CsGSDME cleavage. CsCASP1-cleaved CsGSDME induced pyroptosis, whereas CsCASP3/7-cleaved CsGSDME and F243 mutants induced switching of cell death from apoptosis to pyroptosis. Analysis of 54 teleost GSDME sequences revealed a conserved tetrapeptide motif that fits well to the inherent cleavage site of CASP1. Taken together, the results of our study demonstrate a hitherto, to our knowledge, unrecognized GSDME cleavage mode in teleosts that is clearly different from that in mammals, thus providing an important insight into the activation mechanism of CASP-mediated, GSDM-executed pyroptosis in teleosts.
DOI	10.4049/jimmunol.1900383
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[41876175]###3028; Shandong Major Science and Technology Innovation Project[2018SDKJ0302-2]###2507; National Key Research and Development Program of China[2018YFD0900504]###3029; Taishan Scholar Program of Shandong Province###423; Distinguished Young Scientists Research Fund of the Key Laboratory of Experimental Marine Biology, Chinese Academy of Sciences[KLEMB-DYS03]###3030; National Natural Science Foundation of China[41876175]; Shandong Major Science and Technology Innovation Project[2018SDKJ0302-2]; National Key Research and Development Program of China[2018YFD0900504]; Taishan Scholar Program of Shandong Province; Distinguished Young Scientists Research Fund of the Key Laboratory of Experimental Marine Biology, Chinese Academy of Sciences[KLEMB-DYS03]
WOS研究方向	Immunology
WOS类目	Immunology
WOS记录号	WOS:000481646200027
出版者	AMER ASSOC IMMUNOLOGISTS
引用统计	被引频次：75[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/337002/162382
专题	实验海洋生物学重点实验室
通讯作者	Sun, Li
作者单位	1.Chinese Acad Sci, Ctr Ocean Mega Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao 266071, Peoples R China 2.Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Qingdao 266237, Shandong, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
第一作者单位	中国科学院海洋研究所
通讯作者单位	中国科学院海洋研究所
推荐引用方式 GB/T 7714	Jiang, Shuai,Gu, Hanjie,Zhao, Yan,et al. Teleost Gasdermin E Is Cleaved by Caspase 1, 3, and 7 and Induces Pyroptosis[J]. JOURNAL OF IMMUNOLOGY,2019,203(5):1369-1382.
APA	Jiang, Shuai,Gu, Hanjie,Zhao, Yan,&Sun, Li.(2019).Teleost Gasdermin E Is Cleaved by Caspase 1, 3, and 7 and Induces Pyroptosis.JOURNAL OF IMMUNOLOGY,203(5),1369-1382.
MLA	Jiang, Shuai,et al."Teleost Gasdermin E Is Cleaved by Caspase 1, 3, and 7 and Induces Pyroptosis".JOURNAL OF IMMUNOLOGY 203.5(2019):1369-1382.

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jiang2019.pdf（3183KB）	期刊论文	出版稿	限制开放	CC BY-NC-SA	浏览
Teleost Gasdermin E （2691KB）	期刊论文	出版稿	限制开放	CC BY-NC-SA	浏览