title: Chondroitin sulfates expressed on oligodendrocyte-derived tenascin-R are involved in neural cell recognition. Functional implications during CNS development and regeneration.
abstract: Tenascin-R (TN-R), an extracellular matrix constituent of the central nervous system (CNS), has been implicated in a variety of cell-matrix interactions underlying axon growth inhibition/guidance, myelination and neural cell migration during development and regeneration. Although most of the functional analyses have concentrated exclusively on the role of the core protein, the contribution of TN-R glycoconjugates present on many potential sites for N- and O-glycosylation is presently unknown. Here we provide first evidence that TN-R derived from whole rat brain or cultured oligodendrocytes expresses chondroitin sulfate (CS) glycosaminoglycans (GAGs), i.e., C-4S and C-6S, that are recognized by CS-56, a CS/dermatan sulfate-specific monoclonal antibody. Based on different in vitro approaches utilizing substrate-bound glycoprotein, we found that TN-R-linked CS GAGs (1) promote oligodendrocyte migration from white matter microexplants and increase the motility of oligodendrocyte lineage cells; (2) similar to soluble CS GAGs, induce the formation of glial scar-like structures by cultured cerebral astrocytes; and (3) contribute to the antiadhesive properties of TN-R for neuronal cell adhesion in an F3/F11-independent manner, but not to neurite outgrowth inhibition, by mechanism(s) sensitive to chondroitinase or CS-56 treatments. Furthermore, after transection of the postcommissural fornix in adult rat, CS-bearing TN-R was found to be stably upregulated at the lesion site. Our findings suggest the functional impact of TN-R-linked CS on neural cell adhesion and migration during brain morphogenesis and the contribution of TN-R to astroglial scar formation (CS-dependent) and axon growth inhibition (CS-independent), i.e., suppression of axon regeneration after CNS injury.
authors.affiliation: Department of Biochemistry, Institute of Animal Anatomy and Physiology, University of Bonn, Bonn, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Probstmeier
authors.forename: C C
authors.initials: CC
authors.lastname: Stichel
authors.forename: H W
authors.initials: HW
authors.lastname: Müller
authors.forename: H
authors.initials: H
authors.lastname: Asou
authors.forename: P
authors.initials: P
authors.lastname: Pesheva
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000166:cytology; D002809:Chondroitin Sulfates / Q000378:metabolism*; D005260:Female; D020712:Fornix, Brain / Q000502:physiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009416:Nerve Regeneration / Q000502:physiology; D016501:Neurites / Q000502:physiology; D009836:Oligodendroglia / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D019063:Tenascin / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015815:Cell Adhesion Molecules; D019063:Tenascin; C074638:tenascin R; D002809:Chondroitin Sulfates