<i>Paralichthys olivaceus</i> MLKL-mediated necroptosis is activated by RIPK1/3 and involved in anti-microbial immunity

doi:10.3389/fimmu.2024.1348866

IOCAS-IR > 实验海洋生物学重点实验室

	Paralichthys olivaceus MLKL-mediated necroptosis is activated by RIPK1/3 and involved in anti-microbial immunity
	Hao, Kangwei 1,2,3; Xu, Hang1,2,3 ; Jiang, Shuai 1,2,3; Sun, Li 1,2,3
	2024-01-16
发表期刊	FRONTIERS IN IMMUNOLOGY
ISSN	1664-3224
卷号	15 页码:11
通讯作者	Jiang, Shuai(sjiang@qdio.ac.cn) ; Sun, Li(lsun@qdio.ac.cn)
摘要	Necroptosis is a type of proinflammatory programmed necrosis essential for innate immunity. The receptor interacting protein kinases 1/3 (RIPK1/3) and the substrate mixed lineage kinase domain-like protein (MLKL) are core components of the necroptotic axis. The activation and immunological function of necroptosis in fish remain elusive. Herein, we studied the function and activation of RIPK1/3 (PoRIPK1/3) and MLKL (PoMLKL) in teleost Paralichthys olivaceus. Bacterial infection increased the expression of RIPK1/3 and MLKL. The N-terminal four-helix bundle (4HB) domain of PoMLKL exhibited necroptosis-inducing activity, and the C-terminal pseudokinase domain exerted auto-inhibitory effect on the 4HB domain. PoRIPK3 was capable of phosphorylating the T360/S361 residues in the PoMLKL C-terminal domain and initiated necroptosis, and this necroptosis-inducing activity was enhanced by PoRIPK1. PoRIPK1/3 interacted with PoMLKL in a manner that depended on the RIP homotypic interaction motif (RHIM), and deletion of RHIM from PoRIPK1/3 led to the dissociation of PoRIPK1/3 with PoMLKL. Inhibition of PoMLKL-mediated necroptosis increased Edwardsiella tarda infection in fish cells and tissues, and led to significantly enhanced lethality of the host. Taken together, these results revealed the activation mechanism of PoRIPK1/3-PoMLKL signaling pathway and the immunological function of necroptosis in the immune defense of teleost.
关键词	Paralichthys olivaceus necroptosis RIPK1 RIPK3 MLKL immune defense
DOI	10.3389/fimmu.2024.1348866
收录类别	SCI
语种	英语
资助项目	Key Deployment Project of Centre for Ocean Mega-Research of Science, Chinese Academy of Sciences[COMS2020Q03] ; Science & Technology Innovation Project of Laoshan Laboratory[LSKJ202203000] ; Taishan Scholar Program of Shandong Province[2018] ; Taishan Scholar Program of Shandong Province[2021] ; Youth Innovation Promotion Association CAS[2021204]
WOS研究方向	Immunology
WOS类目	Immunology
WOS记录号	WOS:001153555100001
出版者	FRONTIERS MEDIA SA
WOS关键词	MIXED LINEAGE KINASE ; DOMAIN-LIKE ; MOLECULAR-PATTERNS ; RELEASE ; PHOSPHORYLATION ; DOWNSTREAM ; NECROSIS
引用统计
文献类型	期刊论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/184405
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 Ctr Ocean Megasci, CAS & Shandong Prov Key Lab Expt Marine Biol, Qingdao, Peoples R China 2.Lab Marine Biol & Biotechnol, Laoshan Lab, Qingdao, Peoples R China 3.Univ Chinese Acad Sci, Coll Earth & Planetary Sci, Beijing, Peoples R China
第一作者单位	中国科学院海洋大科学研究中心
通讯作者单位	中国科学院海洋大科学研究中心
推荐引用方式 GB/T 7714	Hao, Kangwei,Xu, Hang,Jiang, Shuai,et al. Paralichthys olivaceus MLKL-mediated necroptosis is activated by RIPK1/3 and involved in anti-microbial immunity[J]. FRONTIERS IN IMMUNOLOGY,2024,15:11.
APA	Hao, Kangwei,Xu, Hang,Jiang, Shuai,&Sun, Li.(2024).Paralichthys olivaceus MLKL-mediated necroptosis is activated by RIPK1/3 and involved in anti-microbial immunity.FRONTIERS IN IMMUNOLOGY,15,11.
MLA	Hao, Kangwei,et al."Paralichthys olivaceus MLKL-mediated necroptosis is activated by RIPK1/3 and involved in anti-microbial immunity".FRONTIERS IN IMMUNOLOGY 15(2024):11.