Cellular adhesion responses to the heparin-binding (HepII) domain of fibronectin require heparan sulfate with specific properties

2.50
Hdl Handle:
http://hdl.handle.net/10541/71336
Title:
Cellular adhesion responses to the heparin-binding (HepII) domain of fibronectin require heparan sulfate with specific properties
Authors:
Mahalingam, Yashithra; Gallagher, John T; Couchman, John R
Abstract:
Cell surface heparan sulfate (HS) proteoglycans are required in development and postnatal repair. Important classes of ligands for HS include growth factors and extracellular matrix macromolecules. For example, the focal adhesion component syndecan-4 interacts with the III(12-14) region of fibronectin (HepII domain) through its HS chains. The fine structure of HS is critical to growth factor responses, and whether this extends to matrix ligands is unknown but is suggested from in vitro experiments. Cell attachment to HepII showed that heparin oligosaccharides of >or=14 sugar residues were required for optimal inhibition. The presence of N-sulfated glucosamine in the HS was essential, whereas 2-O-sulfation of uronic acid or 6-O-sulfation of glucosamine had marginal effects. In the more complex response of focal adhesion formation through syndecan-4, N-sulfates were again required and also glucosamine 6-O-sulfate. The significance of polymer N-sulfation and sulfated domains in HS was confirmed by studies with mutant Chinese hamster ovary cells where heparan sulfation was compromised. Finally, focal adhesion formation was absent in fibroblasts synthesizing short HS chains resulting from a gene trap mutation in one of the two major glucosaminoglycan polymerases (EXT1). Several separate, specific properties of cell surface HS are therefore required in cell adhesion responses to the fibronectin HepII domain.
Affiliation:
Division of Biomedical Sciences, Imperial College London, London SW7 2AZ, United Kingdom.
Citation:
Cellular adhesion responses to the heparin-binding (HepII) domain of fibronectin require heparan sulfate with specific properties. 2007, 282 (5):3221-30 J. Biol. Chem.
Journal:
The Journal of Biological Chemistry
Issue Date:
2-Feb-2007
URI:
http://hdl.handle.net/10541/71336
DOI:
10.1074/jbc.M604938200
PubMed ID:
17130131
Type:
Article
Language:
en
ISSN:
0021-9258
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorMahalingam, Yashithra-
dc.contributor.authorGallagher, John T-
dc.contributor.authorCouchman, John R-
dc.date.accessioned2009-06-23T15:30:22Z-
dc.date.available2009-06-23T15:30:22Z-
dc.date.issued2007-02-02-
dc.identifier.citationCellular adhesion responses to the heparin-binding (HepII) domain of fibronectin require heparan sulfate with specific properties. 2007, 282 (5):3221-30 J. Biol. Chem.en
dc.identifier.issn0021-9258-
dc.identifier.pmid17130131-
dc.identifier.doi10.1074/jbc.M604938200-
dc.identifier.urihttp://hdl.handle.net/10541/71336-
dc.description.abstractCell surface heparan sulfate (HS) proteoglycans are required in development and postnatal repair. Important classes of ligands for HS include growth factors and extracellular matrix macromolecules. For example, the focal adhesion component syndecan-4 interacts with the III(12-14) region of fibronectin (HepII domain) through its HS chains. The fine structure of HS is critical to growth factor responses, and whether this extends to matrix ligands is unknown but is suggested from in vitro experiments. Cell attachment to HepII showed that heparin oligosaccharides of >or=14 sugar residues were required for optimal inhibition. The presence of N-sulfated glucosamine in the HS was essential, whereas 2-O-sulfation of uronic acid or 6-O-sulfation of glucosamine had marginal effects. In the more complex response of focal adhesion formation through syndecan-4, N-sulfates were again required and also glucosamine 6-O-sulfate. The significance of polymer N-sulfation and sulfated domains in HS was confirmed by studies with mutant Chinese hamster ovary cells where heparan sulfation was compromised. Finally, focal adhesion formation was absent in fibroblasts synthesizing short HS chains resulting from a gene trap mutation in one of the two major glucosaminoglycan polymerases (EXT1). Several separate, specific properties of cell surface HS are therefore required in cell adhesion responses to the fibronectin HepII domain.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshBinding Sites-
dc.subject.meshCell Adhesion-
dc.subject.meshCells, Cultured-
dc.subject.meshFibroblasts-
dc.subject.meshFibronectins-
dc.subject.meshHeparin-
dc.subject.meshHeparitin Sulfate-
dc.subject.meshMice-
dc.subject.meshMice, Knockout-
dc.subject.meshRats-
dc.subject.meshRecombinant Proteins-
dc.subject.meshSyndecan-4-
dc.titleCellular adhesion responses to the heparin-binding (HepII) domain of fibronectin require heparan sulfate with specific propertiesen
dc.typeArticleen
dc.contributor.departmentDivision of Biomedical Sciences, Imperial College London, London SW7 2AZ, United Kingdom.en
dc.identifier.journalThe Journal of Biological Chemistryen
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