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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2017
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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. |
format | Online Article Text |
id | pubmed-5415016 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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