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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

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 t...

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Autores principales: Kim, Hyung-Seok, McKnite, Autumn, Xie, Yuanyuan, Christian, Jan L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004582/
https://www.ncbi.nlm.nih.gov/pubmed/29298840
http://dx.doi.org/10.1091/mbc.E17-07-0446
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author Kim, Hyung-Seok
McKnite, Autumn
Xie, Yuanyuan
Christian, Jan L.
author_facet Kim, Hyung-Seok
McKnite, Autumn
Xie, Yuanyuan
Christian, Jan L.
author_sort Kim, Hyung-Seok
collection PubMed
description 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.
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spelling pubmed-60045822018-06-19 Fibronectin type III and intracellular domains of Toll-like receptor 4 interactor with leucine-rich repeats (Tril) are required for developmental signaling Kim, Hyung-Seok McKnite, Autumn Xie, Yuanyuan Christian, Jan L. Mol Biol Cell Brief Reports 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. The American Society for Cell Biology 2018-03-01 /pmc/articles/PMC6004582/ /pubmed/29298840 http://dx.doi.org/10.1091/mbc.E17-07-0446 Text en © 2018 Kim et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0/ This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Brief Reports
Kim, Hyung-Seok
McKnite, Autumn
Xie, Yuanyuan
Christian, Jan L.
Fibronectin type III and intracellular domains of Toll-like receptor 4 interactor with leucine-rich repeats (Tril) are required for developmental signaling
title Fibronectin type III and intracellular domains of Toll-like receptor 4 interactor with leucine-rich repeats (Tril) are required for developmental signaling
title_full Fibronectin type III and intracellular domains of Toll-like receptor 4 interactor with leucine-rich repeats (Tril) are required for developmental signaling
title_fullStr Fibronectin type III and intracellular domains of Toll-like receptor 4 interactor with leucine-rich repeats (Tril) are required for developmental signaling
title_full_unstemmed Fibronectin type III and intracellular domains of Toll-like receptor 4 interactor with leucine-rich repeats (Tril) are required for developmental signaling
title_short Fibronectin type III and intracellular domains of Toll-like receptor 4 interactor with leucine-rich repeats (Tril) are required for developmental signaling
title_sort fibronectin type iii and intracellular domains of toll-like receptor 4 interactor with leucine-rich repeats (tril) are required for developmental signaling
topic Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004582/
https://www.ncbi.nlm.nih.gov/pubmed/29298840
http://dx.doi.org/10.1091/mbc.E17-07-0446
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