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ShanghaiTech University Knowledge Management System
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]) |
ISSN | 1083351X |
卷号 | 294期号:8页码:2744-2756 |
发表状态 | 已发表 |
DOI | 10.1074/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 |
引用统计 | 正在获取...
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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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