Takeda-Uchimura Yoshiko, Nishitsuji Kazuchika, Ikezaki Midori, Akama Tomoya O, Ihara Yoshito, Allain Fabrice, Uchimura Kenji
Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France.
Department of Biochemistry, Wakayama Medical University, Wakayama, Japan.
Front Neuroanat. 2022 Feb 9;16:813841. doi: 10.3389/fnana.2022.813841. eCollection 2022.
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 ). Deficiency in both GlcNAc6ST3 and GlcNAc6ST1, encoded by , 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 -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 , is a major Beta3Gn-T for the synthesis of KS in neuropils and the perineuronal region in the adult brain. Intriguingly, the 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.
硫酸角质素（KS）聚糖共价连接到蛋白聚糖的核心蛋白上。KS在神经纤维网中含量丰富，在生理条件下，在成人大脑神经元周围网阳性神经元的神经元周围区域附近密集存在。我们之前表明，成人大脑中对R - 10G抗体呈阳性的KS的合成是由N - 乙酰葡糖胺 - 6 - 硫酸转移酶3（GlcNAc6ST3；由[具体基因名称]编码）介导的。由[具体基因名称]编码的GlcNAc6ST3和GlcNAc6ST1的缺失完全消除了KS。蛋白酪氨酸磷酸酶受体Z1型（Ptprz1）/磷酸蛋白聚糖被鉴定为KS支架。KS需要通过β1,3 - 乙酰葡糖胺基转移酶（Beta3Gn - T）延伸N - 乙酰葡糖胺。参与成人大脑KS合成的Beta3Gn - T家族成员尚未确定。在本研究中，我们通过基因靶向方法表明，由[具体基因名称]编码的Beta3Gn - T7是成人大脑神经纤维网和神经元周围区域KS合成的主要Beta3Gn - T。有趣的是，[具体基因名称]在少突胶质细胞前体细胞（OPCs）和少突胶质细胞中选择性表达，类似于GlcNAc6ST3。这些结果表明，少突胶质细胞谱系细胞中的Beta3Gn - T7可能通过合成R - 10G阳性的KS修饰蛋白聚糖在成人大脑的神经纤维网和神经元周围网的形成中发挥作用。
