TAG-1/Axonin-1 Is a High-affinity Ligand of Neurocan, Phosphacan/Protein-tyrosine Phosphatase-ζ/β, 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.

Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development

“…Moreover, in Drosophila the CASPR2 homolog neurexin IV binds not only to contactins similar to its vertebrate counterpart (33) but also to other Ig-domain proteins such as neurofascin, wrapper, and roundabout (40)(41)(42). In addition, contactins bind to receptor phospho-tyrosine phosphatases (43,44), which may mediate dendritic growth signaling via the protein tyrosine kinase fyn (45). Strikingly, our initial screen demonstrated that KD of the only known mammalian CASPR2 ligand, contactin-2, produces the opposite phenotype as the CASPR2 KD, a phenotype that can also be rescued with wild-type contactin-2 (Fig.…”

Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene

“…44 The carbonic anhydrase domain interacts with the cell recognition molecule contactin, 51 whereas the spacer region can interact with several other cell adhesion molecules including NrCAM, L1CAM, NCAM, contactin-1 and contactin-2/TAG-1. [52][53][54][55][56] PTPRZ1 gene products are expressed from early developmental to adulthood in glial cells 47,[57][58][59] as well as in certain population of neurons [60][61][62][63] and are implicated in neuron-glial cell interactions that involve on bi-directional signaling, including myelination and node of Ranvier formation, through interactions with neuronal cell adhesion molecules. 55,56 Interestingly, in situ hybridization analysis has shown that PTPRZ1 is expressed in the subventricular zone of the lateral ventricles in early embryos and in adults, in the subgranular zone in the dentate gyrus of the hippocampus of adults, 57,64 and in adult glial progenitor cells, 65 suggesting that PTPRZ1 also has a function in adult stem/progenitor cells.…”

Involvement of Gangliosides in Glycosylphosphatidylinositol-anchored Neuronal Cell Adhesion Molecule TAG-1 Signaling in Lipid Rafts

“…5D). Phosphacan, a neural tissue-specific chondroitin sulfate proteoglycan, is known to be one of the high affinity ligands of TAG-1 (29). Sequential treatment of cerebellar cultures with phosphacan and anti-phosphacan antibody also induced tyrosine phosphorylation of p80 (Fig.…”