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Heparin-fibronectin interactions in the development of extracellular matrix insolubility

Author(s): Raitman, Irene; Huang, Mia L; Williams, Selwyn A; Friedman, Benjamin; Godula, Kamil; et al

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Abstract: During extracellular matrix (ECM) assembly, fibronectin (FN) fibrils are irreversibly converted into a detergent-insoluble form which, through FN's multi-domain structure, can interact with collagens, matricellular proteins, and growth factors to build a definitive matrix. FN also has heparin/heparan sulfate (HS) binding sites. Using HS-deficient CHO cells, we show that the addition of soluble heparin significantly increased the amount of FN matrix that these cells assemble. Sulfated HS glycosaminoglycan (GAG) mimetics similarly increased FN assembly and demonstrated a dependence on GAG sulfation. The length of the heparin chains also plays a role in assembly. Chains of sufficient length to bind to two FN molecules gave maximal stimulation of assembly whereas shorter heparin had less of an effect. Using a decellularized fibroblast matrix for proteolysis, detergent fractionation, and mass spectrometry, we found that the predominant domain within insoluble fibril fragments is FN's major heparin-binding domain HepII (modules III12-14). Multiple HepII domains bind simultaneously to a single heparin chain in size exclusion chromatography analyses. We propose a model in which heparin/HS binding to the HepII domain connects multiple FNs together to facilitate the formation of protein interactions for insoluble fibril assembly.
Publication Date: Apr-2018
Electronic Publication Date: 6-Dec-2017
Citation: Raitman, Irene, Huang, Mia L, Williams, Selwyn A, Friedman, Benjamin, Godula, Kamil, Schwarzbauer, Jean E. (2018). Heparin-fibronectin interactions in the development of extracellular matrix insolubility.. Matrix biology : journal of the International Society for Matrix Biology, 67 (107 - 122). doi:10.1016/j.matbio.2017.11.012
DOI: doi:10.1016/j.matbio.2017.11.012
ISSN: 0945-053X
EISSN: 1569-1802
Pages: 107 - 122
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: Matrix Biology
Version: Author's manuscript

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