Identification of the heparin-binding determinants within fibronectin repeat III1: role in cell spreading and growth
- PMID: 16982604
- DOI: 10.1074/jbc.M608611200
Identification of the heparin-binding determinants within fibronectin repeat III1: role in cell spreading and growth
Abstract
Fibronectins are high molecular mass glycoproteins that circulate as soluble molecules in the blood, and are also found in an insoluble, multimeric form in extracellular matrices throughout the body. Soluble fibronectins are polymerized into insoluble extracellular matrix (ECM) fibrils via a cell-dependent process. Recent studies indicate that the interaction of cells with the ECM form of fibronectin promotes actin organization and cell contractility, increases cell growth and migration, and enhances the tensile strength of artificial tissue constructs; ligation of integrins alone is insufficient to trigger these responses. Evidence suggests that the effect of ECM fibronectin on cell function is mediated in part by a matricryptic heparin-binding site within the first III1 repeat (FNIII1). In this study, we localized the heparin-binding activity of FNIII1 to a cluster of basic amino acids, Arg613, Trp614, Arg615, and Lys617. Site-directed mutagenesis of a recombinant fibronectin construct engineered to mimic the ECM form of fibronectin demonstrates that these residues are also critical for stimulating cell spreading and increasing cell proliferation. Cell proliferation has been tightly correlated with cell area. Using integrin- and heparin-binding fibronectin mutants, we found a positive correlation between cell spreading and growth when cells were submaximally spread on ECM protein-coated surfaces at the time of treatment. However, cells maximally spread on vitronectin or fibronectin still responded to the fibronectin matrix mimetic with an increase in growth, indicating that an absolute change in cell area is not required for the increase in cell proliferation induced by the matricryptic site of FNIII1.
Similar articles
-
A Matricryptic Conformation of the Integrin-Binding Domain of Fibronectin Regulates Platelet-Derived Growth Factor-Induced Intracellular Calcium Release.Cells. 2019 Oct 30;8(11):1351. doi: 10.3390/cells8111351. Cells. 2019. PMID: 31671632 Free PMC article.
-
Chimeric fibronectin matrix mimetic as a functional growth- and migration-promoting adhesive substrate.Biomaterials. 2011 Mar;32(8):2077-87. doi: 10.1016/j.biomaterials.2010.11.050. Epub 2010 Dec 24. Biomaterials. 2011. PMID: 21185596 Free PMC article.
-
Extracellular matrix fibronectin initiates endothelium-dependent arteriolar dilatation via the heparin-binding, matricryptic RWRPK sequence of the first type III repeat of fibrillar fibronectin.J Physiol. 2016 Feb 1;594(3):687-97. doi: 10.1113/JP271478. Epub 2016 Jan 15. J Physiol. 2016. PMID: 26661689 Free PMC article.
-
The role of integrin binding sites in fibronectin matrix assembly in vivo.Curr Opin Cell Biol. 2008 Oct;20(5):502-7. doi: 10.1016/j.ceb.2008.06.001. Epub 2008 Jul 21. Curr Opin Cell Biol. 2008. PMID: 18586094 Review.
-
Fibronectin at a glance.J Cell Sci. 2002 Oct 15;115(Pt 20):3861-3. doi: 10.1242/jcs.00059. J Cell Sci. 2002. PMID: 12244123 Review. No abstract available.
Cited by
-
Cooperative effects of fibronectin matrix assembly and initial cell-substrate adhesion strength in cellular self-assembly.Acta Biomater. 2016 Mar 1;32:198-209. doi: 10.1016/j.actbio.2015.12.032. Epub 2015 Dec 19. Acta Biomater. 2016. PMID: 26712598 Free PMC article.
-
Plasma and cellular fibronectin: distinct and independent functions during tissue repair.Fibrogenesis Tissue Repair. 2011 Sep 16;4:21. doi: 10.1186/1755-1536-4-21. Fibrogenesis Tissue Repair. 2011. PMID: 21923916 Free PMC article.
-
Dairy-Inspired Coatings for Bone Implants from Whey Protein Isolate-Derived Self-Assembled Fibrils.Int J Mol Sci. 2020 Aug 3;21(15):5544. doi: 10.3390/ijms21155544. Int J Mol Sci. 2020. PMID: 32756331 Free PMC article.
-
A Matricryptic Conformation of the Integrin-Binding Domain of Fibronectin Regulates Platelet-Derived Growth Factor-Induced Intracellular Calcium Release.Cells. 2019 Oct 30;8(11):1351. doi: 10.3390/cells8111351. Cells. 2019. PMID: 31671632 Free PMC article.
-
Molecular docking of heparin oligosaccharides with Hep-II heparin-binding domain of fibronectin reveals an interplay between the different positions of sulfate groups.Glycoconj J. 2014 Feb;31(2):161-9. doi: 10.1007/s10719-013-9512-8. Epub 2013 Nov 19. Glycoconj J. 2014. PMID: 24242364
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical