title: Syndecans promote integrin-mediated adhesion of mesenchymal cells in two distinct pathways.
abstract: Syndecans are transmembrane proteoglycans that support integrin-mediated adhesion. Well documented is the contribution of syndecan-4 that interacts through its heparan sulphate chains to promote focal adhesion formation in response to fibronectin domains. This process has requirements for integrin and signaling through the cytoplasmic domain of syndecan-4. Here an alternate pathway mediated by the extracellular domains of syndecans-2 and -4 is characterized that is independent of both heparan sulphate and syndecan signaling. This pathway is restricted to mesenchymal cells and was not seen in any epithelial cell line tested, apart from vascular endothelia. The syndecan ectodomains coated as substrates promoted integrin-dependent attachment, spreading and focal adhesion formation. Syndecan-4 null cells were competent, as were fibroblasts compromised in heparan sulphate synthesis that were unable to form focal adhesions in response to fibronectin. Consistent with actin cytoskeleton organization, the process required Rho-GTP and Rho kinase. While syndecan-2 and -4 ectodomains could both promote integrin-mediated adhesion, their pathways were distinct, as shown by competition assays. Evidence for an indirect interaction of beta1 integrin with both syndecan ectodomains was obtained, all of which suggests a distinct mechanism of integrin-mediated adhesion.
authors.affiliation: National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, Exhibition Road, London SW7 2AZ, UK. j.whiteford@imperial.ac.uk
authors.forename: James R
authors.initials: JR
authors.lastname: Whiteford
authors.forename: Volker
authors.initials: V
authors.lastname: Behrends
authors.forename: Hishani
authors.initials: H
authors.lastname: Kirby
authors.forename: Marion
authors.initials: M
authors.lastname: Kusche-Gullberg
authors.forename: Takashi
authors.initials: T
authors.lastname: Muramatsu
authors.forename: John R
authors.initials: JR
authors.lastname: Couchman
mesh_terms: D000818:Animals; D019556:COS Cells; D002448:Cell Adhesion; D002460:Cell Line; D002522:Chlorocebus aethiops; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D022001:Focal Adhesions / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D019169:Jurkat Cells; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D017434:Protein Structure, Tertiary; D051381:Rats; D053669:Syndecan-2 / Q000737:chemistry / Q000378:metabolism*; D053671:Syndecan-4 / Q000737:chemistry / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D006497:Heparan Sulfate; D016023:Integrins; D053669:Syndecan-2; D053671:Syndecan-4; D054460:rho-Associated Kinases