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TRAF3-interacting JNK-activating modulator promotes inflammation by stimulating translocation of Toll-like receptor 4 to lipid rafts
2019-02-22
发表期刊JOURNAL OF BIOLOGICAL CHEMISTRY (IF:4.0[JCR-2023],4.4[5-Year])
ISSN1083351X
卷号294期号:8页码:2744-2756
发表状态已发表
DOI10.1074/jbc.RA118.003137
摘要

Toll-like receptors (TLRs) are key players of the innate immune system and contribute to inflammation and pathogen clearance. Although TLRs have been extensively studied, it remains unclear how exactly bacterial lipopolysaccharide (LPS)-induced conformational changes of the extracellular domain of the TLRs trigger the dimerization of their intracellular domain across the plasma membrane and thereby stimulate downstream signaling. Here, using LPS-stimulated THP-1-derived macrophages and murine macrophages along with immunoblotting and immunofluorescence and quantitative analyses, we report that in response to inflammatory stimuli, the coiled-coil protein TRAF3-interacting JNK-activating modulator (T3JAM) associates with TLR4, promotes its translocation to lipid rafts, and thereby enhances macrophage-mediated inflammation. T3JAM overexpression increased and T3JAM depletion decreased TLR4 signaling through both the MyD88-dependent pathway and TLR4 endocytosis. Importantly, deletion or mutation of T3JAM to disrupt its coiled-coil-mediated homoassociation abrogated TLR4 recruitment to lipid rafts. Consistently, T3JAM depletion in mice dampened TLR4 signaling and alleviated LPS-induced inflammatory damage. Collectively, our findings reveal an additional molecular mechanism by which TLR4 activity is regulated and suggest that T3JAM may function as a molecular clamp to "tighten up" TLR4 and facilitate its translocation to lipid rafts.

关键词Toll-like receptor 4 (TLR4) inflammation lipopolysaccharide (LPS) lipid raft macrophage innate immunity lipopolysaccharide membrane transfer Toll-like receptor transmembrane protein
收录类别SCI ; SCIE ; EI
语种英语
资助项目Science and Technology Commission of Shanghai Municipality[17YF1422200] ; Science and Technology Commission of Shanghai Municipality[17ZR1435400]
WOS研究方向Biochemistry & Molecular Biology
WOS类目Biochemistry & Molecular Biology
WOS记录号WOS:000459601600015
出版者AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
EI入藏号20191306707305
EI主题词Cell membranes ; Chemical activation ; Macrophages ; Mammals ; Molecular biology
EI分类号Bioengineering and Biology:461 ; Chemical Products Generally:804
WOS关键词RECOGNITION ; INNATE ; TLR4 ; PATTERN ; PROTEIN ; MICRODOMAINS ; ENDOCYTOSIS ; MECHANISMS ; RESPONSES ; MST4
原始文献类型Article
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/30442
专题生命科学与技术学院_博士生
生命科学与技术学院_特聘教授组_周兆才组
生命科学与技术学院_硕士生
通讯作者Jiao, Shi; Zhou, Zhaocai
作者单位
1.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Biochem & Cell Biol, State Key Lab Cell Biol,CAS Ctr Excellence Mol Ce, Shanghai 200031, Peoples R China
2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
3.Fudan Univ, Zhongshan Hosp, Dept Hematol, Shanghai 200032, Peoples R China
4.Fudan Univ, Zhongshan Hosp, Inst Clin Sci, Shanghai 200032, Peoples R China
通讯作者单位生命科学与技术学院
推荐引用方式
GB/T 7714
Li, Yehua,Guan, Jingmin,Wang, Wenjia,et al. TRAF3-interacting JNK-activating modulator promotes inflammation by stimulating translocation of Toll-like receptor 4 to lipid rafts[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2019,294(8):2744-2756.
APA Li, Yehua.,Guan, Jingmin.,Wang, Wenjia.,Hou, Chun.,Zhou, Li.,...&Zhou, Zhaocai.(2019).TRAF3-interacting JNK-activating modulator promotes inflammation by stimulating translocation of Toll-like receptor 4 to lipid rafts.JOURNAL OF BIOLOGICAL CHEMISTRY,294(8),2744-2756.
MLA Li, Yehua,et al."TRAF3-interacting JNK-activating modulator promotes inflammation by stimulating translocation of Toll-like receptor 4 to lipid rafts".JOURNAL OF BIOLOGICAL CHEMISTRY 294.8(2019):2744-2756.
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