特里夫
细胞生物学
内体
TLR4型
信号转导衔接蛋白
溶酶体
信号转导
化学
Toll样受体
生物
受体
生物化学
先天免疫系统
细胞内
酶
作者
Natsuko Tanimura,Shin‐Ichiroh Saitoh,Fumi Matsumoto,Sachiko Akashi‐Takamura,Kensuke Miyake
标识
DOI:10.1016/j.bbrc.2008.01.061
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.
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