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首页> 美国卫生研究院文献>Cell Regulation >A Highlights from MBoC Selection: Fibronectin type III and intracellular domains of Toll-like receptor 4 interactor with leucine-rich repeats (Tril) are required for developmental signaling
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A Highlights from MBoC Selection: Fibronectin type III and intracellular domains of Toll-like receptor 4 interactor with leucine-rich repeats (Tril) are required for developmental signaling

机译：MBoC选择的亮点：发育信号传导需要III型纤连蛋白和Toll样受体4相互作用物与富含亮氨酸的重复序列（Tril）的细胞内结构域

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Toll-like receptor 4 interactor with leucine-rich repeats (Tril) functions as a coreceptor for Toll-like receptors (Tlrs) to mediate innate immune responses in adults. In embryos, Tril signals to promote degradation of the Bmp inhibitor, Smad7, to allow for blood formation. It is not known whether this function requires, or is independent of, Tlrs. In the current studies, we performed a structure–function analysis, which indicated that the fibronectin type III (FN) domain and the intracellular domain of Tril are required to trigger Smad7 degradation in Xenopus embryos. Furthermore, we found evidence suggesting that a Tril deletion mutant lacking the FN domain (Tril∆FN) can dominantly inhibit signaling by endogenous Tril when overexpressed. This finding raises the possibility that the FN domain functions to bind endogenous Tril ligands. We also show that Tril cycles between the cell surface and endosomes and that the Tril extracellular domain, as well as cadherin based cell–cell adhesion, are required for cell surface retention, while the intracellular domain is required for internalization in Xenopus ectodermal explants. Using a CHO cell aggregation assay, we show that, unlike other transmembrane proteins that contain leucine-rich repeats, Tril is not sufficient to mediate homophilic adhesion.
机译：具有丰富亮氨酸重复序列（Tril）的Toll样受体4相互作用体充当Toll样受体（Tlrs）介导成人先天免疫应答的共受体。在胚胎中，Tril发出信号来促进Bmp抑制剂Smad7降解，从而允许血液形成。尚不清楚此功能是否需要或独立于Tlrs。在当前的研究中，我们进行了结构-功能分析，结果表明，III型纤连蛋白（FN）结构域和Tril的细胞内结构域是引发非洲爪蟾胚胎中Smad7降解的必需条件。此外，我们发现证据表明，缺乏FN结构域的Tril缺失突变体（TrilΔFN）在过表达时可以显着抑制内源性Tril的信号传导。该发现增加了FN结构域起到结合内源性TIII配体的作用的可能性。我们还表明，细胞表面和内体之间的Tril循环以及细胞表面保留所需的Tril细胞外结构域以及基于钙粘蛋白的细胞间粘附作用，而非洲爪蟾外胚层外植体的内在化则需要细胞内结构域。使用CHO细胞聚集测定法，我们显示出，与包含富含亮氨酸重复序列的其他跨膜蛋白不同，Tril不足以介导同源性粘附。

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