title: Functional involvement of sciatic nerve-derived versican- and decorin-like molecules and other chondroitin sulphate proteoglycans in ECM-mediated cell adhesion and neurite outgrowth.
abstract: We have previously described two proteoglycans from human sciatic nerve which are immunochemically related to the chondroitin sulphate proteoglycans versican and decorin. The chondroitin sulphate of the versican-like molecule and the core protein of the decorin-like molecule have been found previously to be up-regulated after lesioning the adult mouse sciatic nerve. To investigate if the versican- and decorin-like molecules are involved in cell-extracellular matrix interactions, we studied the effect of both molecules on cell adhesion. The versican- and decorin-like molecules, substrate-coated in a mixture with fibronectin, but not with laminin or collagen types I or IV, inhibited the adhesion of several cell lines, neonatal dorsal root ganglion neurons and Schwann cells. The inhibitory activity was concentration-dependent and mediated by the chondroitin sulphate. Furthermore, when different proteoglycans were incubated with fibronectin, only the versican- and decorin-like molecules and the chondroitin sulphate proteoglycan aggrecan, but not the heparan sulphate proteoglycan perlecan, were able to inhibit fibronectin-mediated cell adhesion. The versican- and decorin-like molecules, substrate-coated alone or in a mixture with fibronectin or laminin, were at most slightly inhibitory to neurite outgrowth from PC12 phaeochromocytoma cells and neonatal dorsal root ganglion neurons. In a solid-phase ligand-binding assay the versican- and decorin-like molecules interacted with fibronectin, but not with laminin or collagen types I and IV. Binding of the versican-like molecule to fibronectin and inhibition of cell adhesion by this molecule was mediated via the heparin and cell-binding domains of fibronectin. These observations suggest that binding of the two proteoglycans to fibronectin is involved in the modulation of adhesion of cells to fibronectin.
authors.affiliation: Department of Neurobiology, Swiss Federal Institute of Technology, Hönggerberg, Zürich.
authors.forename: K H
authors.initials: KH
authors.lastname: Braunewell
authors.forename: P
authors.initials: P
authors.lastname: Pesheva
authors.forename: J B
authors.initials: JB
authors.lastname: McCarthy
authors.forename: L T
authors.initials: LT
authors.lastname: Furcht
authors.forename: B
authors.initials: B
authors.lastname: Schmitz
authors.forename: M
authors.initials: M
authors.lastname: Schachner
mesh_terms: D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D002808:Chondroitin Lyases / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D002809:Chondroitin Sulfates / Q000378:metabolism*; D058575:Decorin; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins; D005353:Fibronectins / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D019763:Heparin Lyase; D006801:Humans; D037181:Lectins, C-Type; D008024:Ligands; D051379:Mice; D009416:Nerve Regeneration / Q000502:physiology; D016501:Neurites / Q000378:metabolism / Q000502:physiology*; D016716:PC12 Cells; D010525:Peripheral Nerves / Q000166:cytology / Q000378:metabolism; D011133:Polysaccharide-Lyases / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D012584:Sciatic Nerve / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D053675:Versicans
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; C546879:Dcn protein, mouse; C546880:Dcn protein, rat; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D037181:Lectins, C-Type; D008024:Ligands; D011509:Proteoglycans; C508322:VCAN protein, human; C508323:Vcan protein, mouse; C508324:Vcan protein, rat; D053675:Versicans; D002809:Chondroitin Sulfates; D002808:Chondroitin Lyases; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase