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Fibronectin matrix as a scaffold for procollagen proteinase binding and collagen processing
The extracellular matrix (ECM) proteins fibronectin (FN) and type I collagen (collagen I) are codistributed in many tissues, and collagens have been shown to depend on an FN matrix for fibrillogenesis. Microscopic analysis of a fibroblast ECM showed colocalization of procollagen I with FN fibrils, a...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The American Society for Cell Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743462/ https://www.ncbi.nlm.nih.gov/pubmed/31242089 http://dx.doi.org/10.1091/mbc.E19-03-0140 |
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author | Saunders, Jared T. Schwarzbauer, Jean E. |
author_facet | Saunders, Jared T. Schwarzbauer, Jean E. |
author_sort | Saunders, Jared T. |
collection | PubMed |
description | The extracellular matrix (ECM) proteins fibronectin (FN) and type I collagen (collagen I) are codistributed in many tissues, and collagens have been shown to depend on an FN matrix for fibrillogenesis. Microscopic analysis of a fibroblast ECM showed colocalization of procollagen I with FN fibrils, and proteolytic cleavage of procollagen to initiate fibril formation was significantly reduced with inhibition of FN matrix assembly. We examined the role of FN matrix in procollagen processing by the C-propeptide proteinase bone morphogenetic protein 1 (BMP-1). We found that BMP-1 binds to a cell-assembled ECM in a dose-dependent manner and that, like procollagen, BMP-1 colocalizes with FN fibrils in the matrix microenvironment. Binding studies with FN fragments identified a binding site in FN’s primary heparin-binding domain. In solution, BMP-1–FN interactions and BMP-1 cleavage of procollagen I were both enhanced by the presence of heparin, suggesting a role for heparin in complex formation during proteolysis. Indeed, addition of heparin enhanced the rate of procollagen cleavage by matrix-bound BMP-1. Our results show that matrix localization of this proteinase facilitates the initiation of collagen assembly and suggest a model in which FN matrix and associated heparan sulfate act as a scaffold to organize enzyme and substrate for procollagen processing. |
format | Online Article Text |
id | pubmed-6743462 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-67434622019-10-16 Fibronectin matrix as a scaffold for procollagen proteinase binding and collagen processing Saunders, Jared T. Schwarzbauer, Jean E. Mol Biol Cell Articles The extracellular matrix (ECM) proteins fibronectin (FN) and type I collagen (collagen I) are codistributed in many tissues, and collagens have been shown to depend on an FN matrix for fibrillogenesis. Microscopic analysis of a fibroblast ECM showed colocalization of procollagen I with FN fibrils, and proteolytic cleavage of procollagen to initiate fibril formation was significantly reduced with inhibition of FN matrix assembly. We examined the role of FN matrix in procollagen processing by the C-propeptide proteinase bone morphogenetic protein 1 (BMP-1). We found that BMP-1 binds to a cell-assembled ECM in a dose-dependent manner and that, like procollagen, BMP-1 colocalizes with FN fibrils in the matrix microenvironment. Binding studies with FN fragments identified a binding site in FN’s primary heparin-binding domain. In solution, BMP-1–FN interactions and BMP-1 cleavage of procollagen I were both enhanced by the presence of heparin, suggesting a role for heparin in complex formation during proteolysis. Indeed, addition of heparin enhanced the rate of procollagen cleavage by matrix-bound BMP-1. Our results show that matrix localization of this proteinase facilitates the initiation of collagen assembly and suggest a model in which FN matrix and associated heparan sulfate act as a scaffold to organize enzyme and substrate for procollagen processing. The American Society for Cell Biology 2019-08-01 /pmc/articles/PMC6743462/ /pubmed/31242089 http://dx.doi.org/10.1091/mbc.E19-03-0140 Text en © 2019 Saunders and Schwarzbauer. “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 | Articles Saunders, Jared T. Schwarzbauer, Jean E. Fibronectin matrix as a scaffold for procollagen proteinase binding and collagen processing |
title | Fibronectin matrix as a scaffold for procollagen proteinase binding and collagen processing |
title_full | Fibronectin matrix as a scaffold for procollagen proteinase binding and collagen processing |
title_fullStr | Fibronectin matrix as a scaffold for procollagen proteinase binding and collagen processing |
title_full_unstemmed | Fibronectin matrix as a scaffold for procollagen proteinase binding and collagen processing |
title_short | Fibronectin matrix as a scaffold for procollagen proteinase binding and collagen processing |
title_sort | fibronectin matrix as a scaffold for procollagen proteinase binding and collagen processing |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743462/ https://www.ncbi.nlm.nih.gov/pubmed/31242089 http://dx.doi.org/10.1091/mbc.E19-03-0140 |
work_keys_str_mv | AT saundersjaredt fibronectinmatrixasascaffoldforprocollagenproteinasebindingandcollagenprocessing AT schwarzbauerjeane fibronectinmatrixasascaffoldforprocollagenproteinasebindingandcollagenprocessing |