Developmental Expression of the Neuron-specific N-Acetylglucosaminyltransferase Vb (GnT-Vb/IX) and Identification of Its in Vivo Glycan Products in Comparison with Those of Its Paralog, GnT-V

Identification of Ectonucleotide Pyrophosphatase/Phosphodiesterase 3 (ENPP3) as a Regulator of N-Acetylglucosaminyltransferase GnT-IX (GnT-Vb)

“…Namely, ENPP3-positive cells are distributed throughout the neuroepithelium in early rat brain development, whereas the spatiotemporal expression is characteristic in the germinal layers of the ventricular zone during later development (51). On the other hand, GnT-IX was recently reported to be distributed throughout the neuroepithelium in early mouse brain development, a finding that is consistent with rat ENPP3, whereas the enzyme was relatively absent from the ventricular zone but was highly expressed in the subventricular zone during later development (27). Thus, it will be necessary to clarify the physiological significance of the ENPP3-mediated GnT-IX inhibition from a spatiotemporal viewpoint in the future.…”

“…The acceptor substrate specificity of this enzyme is broader than that for GnT-V and catalyzes the transfer of a GlcNAc residue in a ␤1,6-linkage from UDP-GlcNAc to ␣-mannose residues in both N-linked and O-mannosyl glycan core structures (26). Recent reports on the functional characteristics of GnT-IX suggest that the enzyme acts almost exclusively on the O-mannosyl glycan as an acceptor substrate in vivo that results in the formation of a brain-specific ␤1,6-branched O-mannosyl glycan (27,28). The ␤1,6-branched O-mannosyl glycan was proposed to be involved in neural cell adhesion and migration through ␤-catenin signaling (29).…”

Neurons and Glia Modify Receptor Protein-tyrosine Phosphatase ζ (RPTPζ)/Phosphacan with Cell-specific O-Mannosyl Glycans in the Developing Brain

“…This result suggests that RPTP/phosphacan is not a substrate for SGK196, AGO61, ␤-1,3-N-acetylgalactosaminyltransferase 2, or LARGE and therefore does not have Core M3 modifications and lamininbinding glycans. The findings from this study support that RPTP/phosphacan is decorated with ␤1,2-elongated and ␤1,6- branched structures, having both Core M1 and Core M2 structures, and is an apparent substrate for POMGnT1 and GnTVb, which agrees with previously published work (14,59,60).…”

“…Recently, it was demonstrated that GnTVb/GnTIX knock-out mice, which lack ␤1,6-branched structures and have reduced Cat-315-immunoreactive RPTP/phosphacan, had no obvious neurological phenotypic abnormalities (60,61). However, a study by Kanekiyo et al (61) demonstrated that GnTVb/GnTIX knock-out mice had impaired astrocyte activation and an enhanced ability to remyelinate axons in a cuprizone-induced demyelinating model.…”

The O-Mannosylation Pathway: Glycosyltransferases and Proteins Implicated in Congenital Muscular Dystrophy

“…6-Branching of the O-mannose is catalyzed by UDP-GlcNAc:mannose ␤1,6-N-acetylglucosaminyltransferase, GnT-Vb (GnT-IX) (60). Although GnT-Vb and O-mannose branching is localized primarily to the brain, making the gene an attractive potential affected target for undiagnosed CMD with neurological complications, mice lacking GnT-Vb alone or in combination with a knock-out of GnT-Va (which can partially compensate for O-Man branching in the absence of GnT-Vb) do not display any gross brain abnormalities or muscular dystrophy (61). Given the recent finding that the 6-phosphomannose structure that was presumably extended with the functional glycan that is LARGE-dependent had an extension with ␤4-GlcNAc instead of ␤2-GlcNAc raises several questions (see Fig.…”