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首页> 外文期刊>Molecular biology of the cell >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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Fibronectin type III and intracellular domains of Toll-like receptor 4 interactor with leucine-rich repeats (Tril) are required for developmental signaling

机译：发育信号传导需要纤维连接蛋白III型与富含含亮氨酸的重复（三叶）的交流剂的互连蛋白域

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摘要

Toll-like receptor 4 interactor with leucine-rich repeats (Tril) functions as a coreceptor for Toll-like receptors (TIrs) 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, Tirs. 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 Delta FN) can dominantly inhibit signaling by endogenous Tril when over-expressed. 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：与富含亮氨酸的重复（三叶）的富含受体4交织剂用作可收费的受体（TIR）的团体，以介导成人的先天免疫应答。在胚胎中，Tril信号促进BMP抑制剂的降解，Smad7，以允许血液形成。尚不知道此功能是否需要，或者独立于TIR。在目前的研究中，我们进行了一种结构函数分析，表明纤连蛋白III型（FN）结构域和三叶细胞内结构域需要在外爪胚轴胚胎中触发SMAD7降解。此外，我们发现证据表明缺乏Fn结构域（三角曲线）的三叶缺失突变体可以在过度表达时通过内源性三轴占主导地位的信号传导。该发现提出了FN结构域的可能性来结合内源性三叶配体。我们还表明细胞表面和内体之间的三个循环，并且细胞表面保持需要细胞表面保留需要细胞内域以及钙粘蛋白的细胞 - 细胞粘附，而细胞内结构域是在外胚层外枝植体的内化所需的。使用CHO细胞聚集测定，我们表明，与含有含亮氨酸的重复的其他跨膜蛋白不同，TRIL不足以介导混合粘附。

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  • 来源
    《Molecular biology of the cell》 |2018年第5期|共9页
  • 作者

    Kim Hyung-Seok; McKnite Autumn; Xie Yuanyuan; Christian Jan L.;

  • 作者单位

    Univ Utah Sch Med Dept Neurobiol &

    Anat &

    Internal Med Div Hematol &

    Hematol Malignancies Salt Lake City UT 84112 USA;

    Univ Utah Sch Med Dept Neurobiol &

    Anat &

    Internal Med Div Hematol &

    Hematol Malignancies Salt Lake City UT 84112 USA;

    Univ Utah Sch Med Dept Neurobiol &

    Anat &

    Internal Med Div Hematol &

    Hematol Malignancies Salt Lake City UT 84112 USA;

    Univ Utah Sch Med Dept Neurobiol &

    Anat &

    Internal Med Div Hematol &

    Hematol Malignancies Salt Lake City UT 84112 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
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