title: TAG-1/axonin-1 is a high-affinity ligand of neurocan, phosphacan/protein-tyrosine phosphatase-zeta/beta, and N-CAM.
abstract: Proteoglycans appear to play an important role in modulating cell-cell and cell-matrix interactions during nervous tissue histogenesis. The nervous tissue-specific chondroitin sulfate proteoglycans neurocan and phosphacan/protein-tyrosine phosphatase-zeta/beta were found to be high-affinity ligands of the neural cell adhesion molecule TAG-1/axonin-1, with dissociation constants of 0.3 nM and 0.04 nM, respectively. Phosphacan binding was decreased by approximately 70% following chondroitinase treatment, whereas binding of neurocan was not affected. The contribution of chondroitin sulfate chains to the binding of neurocan and phosphacan to TAG-1/axonin-1 is therefore the opposite of that previously observed for their binding to two other Ig-superfamily neural cell adhesion molecules, Ng-CAM/L1 and N-CAM. Moreover, whereas phosphacan interactions with certain proteins are mediated at least in part by N-linked oligosaccharides on the proteoglycan, N-deglycosylation of phosphacan had no effect on its binding to TAG-1/axonin-1. In addition to the chondroitin sulfate proteoglycans described above, we have demonstrated that N-CAM is a high-affinity ligand of TAG-1/axonin-1 (Kd approximately 1 nM), and specific binding of TAG-1/axonin-1 to tenascin-C was also observed (Kd approximately 9 nM). Immunocytochemical studies of embryonic and early postnatal nervous tissue showed an overlapping localization of TAG-1/axonin-1 with all four of these ligands, further supporting the biological significance of their ability to interact in vitro.
authors.affiliation: Department of Pharmacology, New York University Medical Center, New York, New York 10016, USA.
authors.forename: P
authors.initials: P
authors.lastname: Milev
authors.forename: P
authors.initials: P
authors.lastname: Maurel
authors.forename: M
authors.initials: M
authors.lastname: Häring
authors.forename: R K
authors.initials: RK
authors.lastname: Margolis
authors.forename: R U
authors.initials: RU
authors.lastname: Margolis
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D058969:Contactin 2; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D037181:Lectins, C-Type; D008024:Ligands; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009420:Nervous System / Q000196:embryology / Q000378:metabolism; D058580:Neurocan; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D017978:Receptors, Growth Factor / Q000378:metabolism; D019063:Tenascin / Q000378:metabolism
chemical_list: C548674:CNTN2 protein, human; D015816:Cell Adhesion Molecules, Neuronal; D011508:Chondroitin Sulfate Proteoglycans; C548676:Cntn2 protein, rat; D058969:Contactin 2; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D008024:Ligands; D009419:Nerve Tissue Proteins; D058580:Neurocan; D011509:Proteoglycans; D017978:Receptors, Growth Factor; D019063:Tenascin; C076817:NCAN protein, human; D010749:Phosphoprotein Phosphatases; C516895:PTPRZ1 protein, human; C516897:Ptprz1 protein, rat; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5