Pufferfish gasdermin Ea is a significant player in the defense against bacterial pathogens

doi:10.1007/s42995-024-00237-x

IOCAS-IR > 实验海洋生物学重点实验室

	Pufferfish gasdermin Ea is a significant player in the defense against bacterial pathogens
	Xu, Hang1,2,3,4 ; Qin, Kunpeng 1,2,3,4; Hao, Kangwei 1,2,3,4; Yuan, Zihao1,2,3,4 ; Sun, Li 1,2,3,4
	2024-06-28
发表期刊	MARINE LIFE SCIENCE & TECHNOLOGY
ISSN	2096-6490
页码	13
通讯作者	Yuan, Zihao(yuanzihao@qdio.ac.cn) ; Sun, Li(lsun@qdio.ac.cn)
摘要	Gasdermins (GSDMs) are proteins cleaved by caspase (CASP) to trigger pyroptosis. In teleosts, pyroptosis is mediated by gasdermin E (GSDME). The Pufferfish, Takifugu rubripes, possesses two GSDME orthologs: named TrGSDMEa and TrGSDMEb. TrGSDMEa is cleaved by CASP3/7 to liberate the N-terminal (NT) domain that can trigger pyroptosis in mammalian cells. However, the biological function of TrGSDMEa in pufferfish is unknown, and TrGSDMEb is poorly studied. We found that TrGSDMEb was cleaved by CASP1/3/6/7/8, but the resulting NT domain, despite its similarity to TrGSDMEa-NT domain in sequence and structure, failed to induce pyroptosis. TrGSDMEa and TrGSDMEb exhibited similar expression patterns in pufferfish under normal physiological conditions but were up- and downregulated, respectively, in expression during Vibrio harveyi and Edwardsiella tarda infection. Bacterial infection induced the activation of TrGSDMEa and CASP3/7 in pufferfish cells, resulting in pyroptosis accompanied with IL-1 beta production and maturation. Inhibition of TrGSDMEa-mediated pyroptosis via TrCASP3/7 reduced the death of pufferfish cells and augmented bacterial dissemination in fish tissues. Structure-oriented mutagenesis identified 16 conserved residues in teleost GSDMEa that were required for the pore formation or auto-inhibition of GSDMEa. This study illustrates the role of GSDMEa-mediated pyroptosis in teleost defense against bacterial pathogens and provides new insights into the structure-based function of vertebrate GSDME.
关键词	GSDME Caspase Takifugu rubripes Bacterial infection Immune defense
DOI	10.1007/s42995-024-00237-x
收录类别	SCI
语种	英语
资助项目	Science & Technology Innovation Project of Laoshan Laboratory[LSKJ202203000] ; Postdoctoral Fellowship Program of CPSF[GZC20232709] ; China Postdoctoral Science Foundation[2023TQ0356]
WOS研究方向	Marine & Freshwater Biology
WOS类目	Marine & Freshwater Biology
WOS记录号	WOS:001258613400001
出版者	SPRINGERNATURE
WOS关键词	INFLAMMATORY CASPASES ; PYROPTOSIS ; CLEAVAGE ; ACTIVATION ; GENOME ; FAMILY ; PORE
引用统计
文献类型	期刊论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/186408
专题	实验海洋生物学重点实验室
通讯作者	Yuan, Zihao; Sun, Li
作者单位	1.Chinese Acad Sci, Qingdao 266071, Peoples R China 2.Chinese Acad Sci, Inst Oceanol, CAS Ctr Ocean Mega Sci, Shandong Prov Key Lab Expt Marine Biol, Qingdao 266071, Peoples R China 3.Laoshan Lab, Lab Marine Biol & Biotechnol, Qingdao 266237, Peoples R China 4.Univ Chinese Acad Sci, Sch Marine Sci, Qingdao 266400, 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	Xu, Hang,Qin, Kunpeng,Hao, Kangwei,et al. Pufferfish gasdermin Ea is a significant player in the defense against bacterial pathogens[J]. MARINE LIFE SCIENCE & TECHNOLOGY,2024:13.
APA	Xu, Hang,Qin, Kunpeng,Hao, Kangwei,Yuan, Zihao,&Sun, Li.(2024).Pufferfish gasdermin Ea is a significant player in the defense against bacterial pathogens.MARINE LIFE SCIENCE & TECHNOLOGY,13.
MLA	Xu, Hang,et al."Pufferfish gasdermin Ea is a significant player in the defense against bacterial pathogens".MARINE LIFE SCIENCE & TECHNOLOGY (2024):13.