Abstract
Keratan sulfate (KS) glycan is covalently attached to a core protein of proteoglycans. KS is abundant in neuropils and presents densely in close proximity to the perineuronal region of the perineuronal net-positive neurons in the adult brain under physiological conditions. We previously showed that the synthesis of KS positive for the R-10G antibody in the adult brain is mediated by GlcNAc-6-sulfotransferase 3 (GlcNAc6ST3; encoded by Chst5). Deficiency in both GlcNAc6ST3 and GlcNAc6ST1, encoded by Chst2, completely abolished KS. Protein-tyrosine phosphatase receptor type z1 (Ptprz1)/phosphacan was identified as a KS scaffold. KS requires the extension of GlcNAc by β1,3 N-acetylglucosaminyltransferase (Beta3Gn-T). Members of the Beta3Gn-T family involved in the synthesis of adult brain KS have not been identified. In this study, we show by a method of gene targeting that Beta3Gn-T7, encoded by B3gnt7, is a major Beta3Gn-T for the synthesis of KS in neuropils and the perineuronal region in the adult brain. Intriguingly, the B3gnt7 gene is selectively expressed in oligodendrocyte precursor cells (OPCs) and oligodendrocytes similar to that of GlcNAc6ST3. These results indicate that Beta3Gn-T7 in oligodendrocyte lineage cells may play a role in the formation of neuropils and perineuronal nets in the adult brain through the synthesis of R-10G-positive KS-modified proteoglycan.
Highlights
Interstitial extracellular components such as proteoglycans, hyaluronan, and tenascins account for approximately 20% of the total volume of the adult brain (Nicholson and Rice, 1986)
We show that Beta3Gn-T7, known as B3GNT7 encoded by B3gnt7, is essential for the synthesis of R-10G-positive Keratan sulfate (KS) in the adult brain and that cell types that selectively express Beta3Gn-T7 are oligodendrocyte precursor cells (OPCs) and newly formed oligodendrocytes similar to those for GlcNAc6ST3
As we reported previously (Narentuya et al, 2019), R-10G staining signals in the neuropils and perineuronal nets (PNNs) proximities were seen within the whole area of the cerebral cortices
Summary
Interstitial extracellular components such as proteoglycans, hyaluronan, and tenascins account for approximately 20% of the total volume of the adult brain (Nicholson and Rice, 1986). (ii) Microglial 5D4-positive KS proteoglycan is expressed in adult brains of patients and disease models of rats and mice The expression of this molecule is induced in activated microglia under pathological conditions (Jones and Tuszynski, 2002; Fan et al, 2007; Xu et al, 2008; Hirano et al, 2013; Foyez et al, 2015; Zhang et al, 2017; Ohgomori and Jinno, 2020) and relies on GlcNAc-6-sulfotransferase (GlcNAc6ST) 1 (Uchimura et al, 1998; Zhang et al, 2017). We show that Beta3Gn-T7, known as B3GNT7 encoded by B3gnt, is essential for the synthesis of R-10G-positive KS in the adult brain and that cell types that selectively express Beta3Gn-T7 are OPCs and newly formed oligodendrocytes similar to those for GlcNAc6ST3. Beta3Gn-T7 may mediate the synthesis of R-10G-positive KS-modified Ptprz1/phosphacan, a PNN component, in concerted actions with GlcNAc6ST3
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