Roles for LPS-dependent interaction and relocation of TLR4 and TRAM in TRIF-signaling

被引：215

作者：

Tanimura, Natsuko ^{[1
,2
]}

Saitoh, Shinichiroh ^{[1
]}

Matsumoto, Fumi ^{[1
]}

Akashi-Takamura, Sachiko ^{[1
]}

Miyake, Kensuke ^{[1
]}

机构：

[1] Univ Tokyo, Inst Med Sci, Div Infect Genet, Dept Microbiol & Immunol,Minato Ku, Tokyo 1088639, Japan

[2] Japan Soc Promot Sci, Tokyo 1028472, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 368卷 / 01期

基金：

日本学术振兴会;

关键词：

innate immunity; lipopolysaccharide; toll-like receptor; interferon;

D O I：

10.1016/j.bbrc.2008.01.061

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Toll-like receptor 4 (TLR4) activates two distinct signaling pathways inducing production of proinflammatory cytokines or type I interferons (IFNs), respectively. MyD88 and TIRAP/Mal are essential adaptor molecules for the former but not for the latter pathway. In contrast, TRIF/TICAM-1 and TRAM/TICAM-2 are essential for both. TIRAP is a sorting adaptor molecule recruiting MyD88 to activated TLR4 in the plasma membrane. TRAM is thought to bridge between TLR4 and TRIF by physical association. Little is known, however, how TRAM interacts with TLR4 or with TRIF during LPS response. Here, we show that TRAM recruits TRIF to the plasma membrane. Moreover, LPS induces upregulation of TLR4-association with TRAM and their subsequent translocation into endosome/lysosome. The internalized signaling complex consisting of TLR4 and TRAM colocalizes with TRAF3, a signaling molecule downstream of TRIF, in endosome/lysosome. These results suggest that TLR4 activates TRIF-signaling in endosome/lysosome after relocation from the cell surface. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：94 / 99

页数：6

共 22 条

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