Alpha-mannosidase-II deficiency results in dyserythropoiesis and unveils an alternate pathway in oligosaccharide biosynthesis
Alpha-mannosidase-II deficiency results in dyserythropoiesis and unveils an alternate pathway in oligosaccharide biosynthesis
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DOI：
10.1016/s0092-8674(00)80322-0
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发表时间：
1997-07-11
期刊：
影响因子：
64.5
通讯作者：
Marth, JD
中科院分区：
文献类型：
--
作者：
Chui, D;OhEda, M;Marth, JD
α-甘露糖苷酶-II（α M-II）催化复杂天冬酰胺连接（N-连接）寡糖（N-聚糖）生物合成中的第一个关键步骤。α M-II的遗传缺陷应消除复杂的N-聚糖的生产，据报道，α M-II抑制苦马豆素。我们发现，缺乏功能性α M-II基因的小鼠发生红细胞生成障碍性贫血，同时伴有红细胞复合物N-聚糖的丢失。出乎意料的是，非红系细胞类型通过包含不同α-甘露糖苷酶的替代途径继续产生复合N-聚糖。这些研究揭示了N-连接寡糖生物合成中的细胞类型特异性变化以及α M-II在红系复合物N-聚糖形成中的重要作用。小鼠中α M-II缺乏症与人类先天性红细胞生成不良性贫血II型相关的表型。
Alpha-mannosidase-II (alpha M-II) catalyzes the first committed step in the biosynthesis of complex asparagine-linked (N-linked) oligosaccharides (N-glycans). Genetic deficiency of alpha M-II should abolish complex N-glycan production as reportedly does inhibition of alpha M-II by swainsonine. We find that mice lacking a functional alpha M-II gene develop a dyserythropoietic anemia concurrent with loss of erythrocyte complex N-glycans. Unexpectedly, nonerythroid cell types continued to produce complex N-glycans by an alternate pathway comprising a distinct alpha-mannosidase. These studies reveal cell-type-specific variations in N-linked oligosaccharide biosynthesis and an essential role for alpha M-II in the formation of erythroid complex N-glycans. alpha M-II deficiency elicits a phenotype in mice that correlates with human congenital dyserythropoietic anemia type II.