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TGF-β triggers rapid fibrillogenesis via a novel TβRII-dependent fibronectin-trafficking mechanism

Fibronectin (FN) is a critical regulator of extracellular matrix (ECM) remodeling through its availability and stepwise polymerization for fibrillogenesis. Availability of FN is regulated by its synthesis and turnover, and fibrillogenesis is a multistep, integrin-dependent process essential for cell...

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Autores principales: Varadaraj, Archana, Jenkins, Laura M., Singh, Priyanka, Chanda, Anindya, Snider, John, Lee, N. Y., Amsalem-Zafran, Ayelet R., Ehrlich, Marcelo, Henis, Yoav I., Mythreye, Karthikeyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415016/
https://www.ncbi.nlm.nih.gov/pubmed/28298487
http://dx.doi.org/10.1091/mbc.E16-08-0601
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author Varadaraj, Archana
Jenkins, Laura M.
Singh, Priyanka
Chanda, Anindya
Snider, John
Lee, N. Y.
Amsalem-Zafran, Ayelet R.
Ehrlich, Marcelo
Henis, Yoav I.
Mythreye, Karthikeyan
author_facet Varadaraj, Archana
Jenkins, Laura M.
Singh, Priyanka
Chanda, Anindya
Snider, John
Lee, N. Y.
Amsalem-Zafran, Ayelet R.
Ehrlich, Marcelo
Henis, Yoav I.
Mythreye, Karthikeyan
author_sort Varadaraj, Archana
collection PubMed
description Fibronectin (FN) is a critical regulator of extracellular matrix (ECM) remodeling through its availability and stepwise polymerization for fibrillogenesis. Availability of FN is regulated by its synthesis and turnover, and fibrillogenesis is a multistep, integrin-dependent process essential for cell migration, proliferation, and tissue function. Transforming growth factor β (TGF-β) is an established regulator of ECM remodeling via transcriptional control of ECM proteins. Here we show that TGF-β, through increased FN trafficking in a transcription- and SMAD-independent manner, is a direct and rapid inducer of the fibrillogenesis required for TGF-β–induced cell migration. Whereas TGF-β signaling is dispensable for rapid fibrillogenesis, stable interactions between the cytoplasmic domain of the type II TGF-β receptor (TβRII) and the FN receptor (α5β1 integrin) are required. We find that, in response to TGF-β, cell surface–internalized FN is not degraded by the lysosome but instead undergoes recycling and incorporation into fibrils, a process dependent on TβRII. These findings are the first to show direct use of trafficked and recycled FN for fibrillogenesis, with a striking role for TGF-β in this process. Given the significant physiological consequences associated with FN availability and polymerization, our findings provide new insights into the regulation of fibrillogenesis for cellular homeostasis.
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spelling pubmed-54150162017-07-16 TGF-β triggers rapid fibrillogenesis via a novel TβRII-dependent fibronectin-trafficking mechanism Varadaraj, Archana Jenkins, Laura M. Singh, Priyanka Chanda, Anindya Snider, John Lee, N. Y. Amsalem-Zafran, Ayelet R. Ehrlich, Marcelo Henis, Yoav I. Mythreye, Karthikeyan Mol Biol Cell Articles Fibronectin (FN) is a critical regulator of extracellular matrix (ECM) remodeling through its availability and stepwise polymerization for fibrillogenesis. Availability of FN is regulated by its synthesis and turnover, and fibrillogenesis is a multistep, integrin-dependent process essential for cell migration, proliferation, and tissue function. Transforming growth factor β (TGF-β) is an established regulator of ECM remodeling via transcriptional control of ECM proteins. Here we show that TGF-β, through increased FN trafficking in a transcription- and SMAD-independent manner, is a direct and rapid inducer of the fibrillogenesis required for TGF-β–induced cell migration. Whereas TGF-β signaling is dispensable for rapid fibrillogenesis, stable interactions between the cytoplasmic domain of the type II TGF-β receptor (TβRII) and the FN receptor (α5β1 integrin) are required. We find that, in response to TGF-β, cell surface–internalized FN is not degraded by the lysosome but instead undergoes recycling and incorporation into fibrils, a process dependent on TβRII. These findings are the first to show direct use of trafficked and recycled FN for fibrillogenesis, with a striking role for TGF-β in this process. Given the significant physiological consequences associated with FN availability and polymerization, our findings provide new insights into the regulation of fibrillogenesis for cellular homeostasis. The American Society for Cell Biology 2017-05-01 /pmc/articles/PMC5415016/ /pubmed/28298487 http://dx.doi.org/10.1091/mbc.E16-08-0601 Text en © 2017 Varadaraj et al. 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 (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Varadaraj, Archana
Jenkins, Laura M.
Singh, Priyanka
Chanda, Anindya
Snider, John
Lee, N. Y.
Amsalem-Zafran, Ayelet R.
Ehrlich, Marcelo
Henis, Yoav I.
Mythreye, Karthikeyan
TGF-β triggers rapid fibrillogenesis via a novel TβRII-dependent fibronectin-trafficking mechanism
title TGF-β triggers rapid fibrillogenesis via a novel TβRII-dependent fibronectin-trafficking mechanism
title_full TGF-β triggers rapid fibrillogenesis via a novel TβRII-dependent fibronectin-trafficking mechanism
title_fullStr TGF-β triggers rapid fibrillogenesis via a novel TβRII-dependent fibronectin-trafficking mechanism
title_full_unstemmed TGF-β triggers rapid fibrillogenesis via a novel TβRII-dependent fibronectin-trafficking mechanism
title_short TGF-β triggers rapid fibrillogenesis via a novel TβRII-dependent fibronectin-trafficking mechanism
title_sort tgf-β triggers rapid fibrillogenesis via a novel tβrii-dependent fibronectin-trafficking mechanism
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415016/
https://www.ncbi.nlm.nih.gov/pubmed/28298487
http://dx.doi.org/10.1091/mbc.E16-08-0601
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