Increased bisecting and core-fucosylated N-glycans on mutant human amyloid precursor proteins
Increased bisecting and core-fucosylated N-glycans on mutant human amyloid precursor proteins
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DOI：
10.1007/s10719-008-9140-x
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发表时间：
2008-11-01
影响因子：
3
通讯作者：
Endo, Tamao
中科院分区：
文献类型：
--
作者：
Akasaka-Manya, Keiko;Manya, Hiroshi;Endo, Tamao
糖蛋白聚糖的改变通常会改变糖蛋白的各种特性。为了了解 N-糖基化在早发家族性阿尔茨海默病 (AD) 发病机制和 β-淀粉样蛋白 (Aβ) 产生中的重要性，我们检查了家族性 AD 中发现的淀粉样蛋白前体蛋白 (APP) 基因的突变是否影响 APP 上的 N-聚糖。我们纯化了转染的 C17 细胞产生的野生型和突变型人类 APP（瑞典型和伦敦型）的分泌形式，并确定了这三种重组 APP 的 N-聚糖结构。尽管三种 APP 的主要 N-聚糖种类相似，但与野生型 APP 相比，两种突变型 APP 均含有较高含量的二等分 N-乙酰氨基葡萄糖和核心岩藻糖残基。这些结果表明，APP 多肽主链中的家族性 AD 突变会影响所附着的 N-聚糖的加工；然而，N-糖基化的这些变化是否影响 Aβ 的产生仍有待确定。
Alteration of glycoprotein glycans often changes various properties of the glycoprotein. To understand the significance of N-glycosylation in the pathogenesis of early-onset familial Alzheimer's disease (AD) and in beta-amyloid (A beta) production, we examined whether the mutations in the amyloid precursor protein (APP) gene found in familial AD affect the N-glycans on APP. We purified the secreted forms of wild-type and mutant human APPs (both the Swedish type and the London type) produced by transfected C17 cells and determined the N-glycan structures of these three recombinant APPs. Although the major N-glycan species of the three APPs were similar, both mutant APPs contained higher contents of bisecting N-acetylglucosamine and core-fucose residues as compared to wild-type APP. These results demonstrate that familial AD mutations in the polypeptide backbone of APP can affect processing of the attached N-glycans; however, whether these changes in N-glycosylation affect A beta production remains to be established.