REVERSIBLE DEFECTS IN O-LINKED GLYCOSYLATION AND LDL RECEPTOR EXPRESSION IN A UDP-GAL/UDP-GAINAC 4-EPIMERASE DEFICIENT MUTANT
REVERSIBLE DEFECTS IN O-LINKED GLYCOSYLATION AND LDL RECEPTOR EXPRESSION IN A UDP-GAL/UDP-GAINAC 4-EPIMERASE DEFICIENT MUTANT
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DOI：
10.1016/0092-8674(86)90841-x
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发表时间：
1986-03-14
期刊：
影响因子：
64.5
通讯作者：
KRIEGER, M
中科院分区：
文献类型：
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作者：
KINGSLEY, DM;KOZARSKY, KF;KRIEGER, M
我们先前分离出一种不寻常的仓鼠突变体（IDID），该突变体（IDID）不表达LDL受体活性，除非它与其他细胞共培养或以高浓度的血清生长。现在，我们表明IDID细胞缺乏酶UDP-半乳糖和UDP-N-乙酰乳糖胺（GalNAC）4- epimerase。当IDID细胞在基于葡萄糖的培养基中生长时，它们无法合成足够的UDP-乳糖果和UDP-GALNAC，以使糖脂和糖蛋白正常合成。 4-期间酶缺乏症解释了先前在IDID细胞中观察到的所有糖基化缺陷，包括产生异常的LDL受体。 IDID细胞的所有异常表型都可以通过外源性半乳糖和GalNAC充分校正。这些糖对LDL受体活性的单独影响表明O连锁的碳水化合物链对于受体稳定性至关重要。 IDID细胞可能可用于许多蛋白质，蛋白聚糖和含有半乳糖或GalNAC的糖脂的结构和功能研究。
We previously isolated an unusual hamster cell mutant (IdID) that does not express LDL receptor activity unless it is cocultivated with other cells or grown in high concentrations of serum. We now show that IdID cells are deficient in the enzyme UDP-galactose and UDP-N-acetylgalactosamine (GalNAc) 4-epimerase. When IdID cells are grown in glucose-based media, they cannot synthesize enough UDP-galactose and UDP-GalNAc to allow normal synthesis of glycolipids and glycoproteins. The 4-epimerase deficiency accounts for all glycosylation defects previously observed in IdID cells, including production of abnormal LDL receptors. All abnormal phenotypes of IdID cells can be fully corrected by exogenous galactose and GalNAc. The separate effects of these sugars on LDL receptor activity suggest that O-linked carbohydrate chains are crucial for receptor stability. IdID cells may be useful for structural and functional studies of many proteins, proteoglycans, and glycolipids containing galactose or GalNAc.