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Mol Biol Cell. 2017 May 1;28(9):1195-1207. doi: 10.1091/mbc.E16-08-0601. Epub 2017 Mar 15.

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

Author information

1
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208.
2
Department of Environmental Health Sciences, University of South Carolina, Columbia, SC 29201.
3
Division of Pharmacology, College of Pharmacy, Ohio State University, Columbus, OH 43210.
4
Department of Neurobiology, Tel Aviv University, Tel Aviv 69978, Israel.
5
Department of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
6
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208 mythreye@sc.edu.
7
Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC 29208.

Abstract

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.

PMID:
28298487
PMCID:
PMC5415016
DOI:
10.1091/mbc.E16-08-0601
[Indexed for MEDLINE]
Free PMC Article

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