EFFICIENT ROUTING OF GLUCOCEREBROSIDASE TO LYSOSOMES REQUIRES COMPLEX OLIGOSACCHARIDE CHAIN FORMATION

EFFICIENT ROUTING OF GLUCOCEREBROSIDASE TO LYSOSOMES REQUIRES COMPLEX OLIGOSACCHARIDE CHAIN FORMATION
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DOI:
10.1016/s0006-291x(86)80194-2
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发表时间:
1986-12-15
影响因子:
3.1
通讯作者:
SCHRAM, AW
SCHRAM, AW
中科院分区:
生物学4区
文献类型:
--
作者:
AERTS, JMFG;BRUL, S;SCHRAM, AW

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在单核细胞系U937中研究了膜相关溶酶体酶葡萄糖脑苷脂酶的生物合成和细胞内转运。此外,寡糖修剪抑制剂苦马豆素或脱氧mannojirimycin的文化导致葡萄糖脑苷脂酶的细胞内活性增加。这是由于防止了酶的溶酶体降解。当对照细胞的匀浆在Percoll梯度葡萄糖脑苷脂酶(如β-葡萄糖脑苷脂酶)上分级时,氨基己糖苷酶呈双峰分布,一个在低密度处,一个在高密度处。当将在寡糖修整抑制剂存在下培养的细胞的匀浆分级分离时,氨基己糖苷酶仍然分布在两个峰中,但葡萄糖脑苷脂酶主要存在于也含有半乳糖基转移酶活性的低密度级分中。它的结论是,复杂型寡糖链的形成所需的有效路由的葡萄糖脑苷脂酶的溶酶体在U937细胞。
The biosynthesis and intracellular transport of the membrane-associated lysosomal enzyme glucocerebrosidase was studied in the monoblast cell line U937. Addition to the cultures of the oligosaccharide trimming inhibitors swainsonine or deoxymannojirimycin led to an increased intracellular activity of glucocerebrosidase. This was due to prevention of the lysosomal degradation of the enzyme. When homogenates of control cells were fractionated on Percoll gradients glucocerebrosidase, like .beta.-hexosaminidase, was distributed in two peaks, one at low density and one at high density. When homogenates of cells cultured in the presence of oligosaccharide trimming inhibitors were fractionated .beta.-hexosaminidase was still distributed in two peaks but glucocerebrosidase was found mainly in low density fractions also containing galactosyltransferase activity. It is concluded that complex type oligosaccharide chain formation is required for efficient routing of glucocerebrosidase to the lysosomes in U937 cells.