Major glycan structure underlying expression of the Lewis X epitope in the developing brain is O-mannose-linked glycans on phosphacan/RPTPβ
Major glycan structure underlying expression of the Lewis X epitope in the developing brain is O-mannose-linked glycans on phosphacan/RPTPβ
复制标题
发育中大脑中 Lewis X 表位表达的主要聚糖结构是磷酸聚糖/RPTPβ 上的 O-甘露糖连接聚糖
DOI：
10.1093/glycob/cwu118
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发表时间：
2015
期刊：
影响因子：
4.3
通讯作者：
Shogo Oka
中科院分区：
文献类型：
--
作者：
Shohei Yaji;Hiroshi Manya;Naoki Nakagawa;Hiromu Take matsu;Tamao Endo;Reiji Kannagi;Toru Yoshihara;Masahide Asano;Shogo Oka
糖基化是一种主要的蛋白质修饰。尽管蛋白质在从内质网运输到高尔基体的过程中被糖基化/被几种糖基转移酶进一步调节，但仅在有限数量的蛋白质上检测到某种聚糖表位。在这些聚糖表位中，刘易斯X在发育中的脑的早期高度表达，并且在细胞-细胞相互作用中起重要作用。刘易斯X表位由三糖（Galβ1-4（Fucα1-3）GlcNAc）组成，该表位表达的关键酶是α 1，3-岩藻糖基转移酶9。然而，负责形成刘易斯X表位及其主要载体蛋白的支架聚糖结构在神经系统中尚未完全表征。我们发现刘易斯X抗原表位主要表达在发育中的小鼠脑中的磷酸蛋白聚糖/受体蛋白酪氨酸磷酸酶β（RPTPβ）上。β 1，4-半乳糖基转移酶2（β 4 GalT 2）基因缺陷小鼠的刘易斯X表位表达显著降低，表明β 4 GalT 2是刘易斯X表位所需的主要半乳糖基转移酶。我们还发现，由于O-甘露糖β 1，2-N-乙酰葡糖胺转移酶1蛋白的敲除，刘易斯X表位几乎消失，这表明O-甘露糖基化聚糖负责呈递刘易斯X表位。由于phosphacan/RPTPβ上的O-甘露糖基化聚糖也可以提呈神经系统特异性表达的另一种聚糖表位--人自然杀伤细胞-1，我们的研究结果揭示了O-甘露糖基化聚糖链在脑内功能性聚糖表位提呈中的重要性。
Glycosylation is a major protein modification. Although proteins are glycosylated/further modulated by several glycosyltransferases during trafficking from the endoplasmic reticulum to the Golgi apparatus, a certain glycan epitope has only been detected on a limited number of proteins. Of these glycan epitopes, Lewis X is highly expressed in the early stage of a developing brain and plays important roles in cell–cell interaction. The Lewis X epitope is comprised of a trisaccharide (Galβ1-4 (Fucα1-3) GlcNAc), and a key enzyme for the expression of this epitope is α1,3-fucosyltransferase 9. However, the scaffolding glycan structure responsible for the formation of the Lewis X epitope as well as its major carrier protein has not been fully characterized in the nervous system. Here we showed that the Lewis X epitope was mainly expressed on phosphacan/receptor protein tyrosine phosphatase β (RPTPβ) in the developing mouse brain. Expression of the Lewis X epitope was markedly reduced inβ1,4-galactosyltransferase 2(β4GalT2)gene-deficient mice, which indicated that β4GalT2 is a major galactosyltransferase required for the Lewis X epitope. We also showed that the Lewis X epitope almost disappeared due to the knockout ofprotein O-mannose β1,2-N-acetylglucosaminyltransferase 1, anN-acetylglucosaminyltransferase essential for the synthesis ofO-mannosylated glycans, which indicated that theO-mannosylated glycan is responsible for presenting the Lewis X epitope. SinceO-mannosylated glycans on phosphacan/RPTPβ could also present human natural killer-1, another glycan epitope specifically expressed in the nervous system, our results revealed the importance ofO-mannosylated glycan chains in the presentation of functional glycan epitopes in the brain.