GLUCOSE REMOVAL FROM N-LINKED OLIGOSACCHARIDES IS REQUIRED FOR EFFICIENT MATURATION OF CERTAIN SECRETORY GLYCOPROTEINS FROM THE ROUGH ENDOPLASMIC-RETICULUM TO THE GOLGI-COMPLEX
GLUCOSE REMOVAL FROM N-LINKED OLIGOSACCHARIDES IS REQUIRED FOR EFFICIENT MATURATION OF CERTAIN SECRETORY GLYCOPROTEINS FROM THE ROUGH ENDOPLASMIC-RETICULUM TO THE GOLGI-COMPLEX
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DOI：
10.1083/jcb.98.5.1720
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发表时间：
1984-01-01
影响因子：
7.8
通讯作者：
KONG, N
中科院分区：
文献类型：
--
作者：
LODISH, HF;KONG, N
1-脱氧野生霉素是糖苷酶I和糖苷酶II的特异性抑制剂，糖苷酶I和糖苷酶II是第一种酶，在将N-连接的寡糖转移到粗面内质网中的多肽后处理它们。在脉冲追逐实验中，1-脱氧野生霉素显著降低人肝癌细胞分泌α1-抗胰蛋白酶和α1-抗糜蛋白酶的速率，但对糖蛋白C3和转铁蛋白或白蛋白的分泌影响不大。通过平衡梯度离心法判断，1-脱氧野吉霉素导致α1-抗胰蛋白酶和α1-抗糜蛋白酶在粗面内质网中积聚。在1-脱氧诺吉霉素存在下合成的细胞相关α1-抗胰蛋白酶和α1-抗糜蛋白酶上的寡糖对内糖苷酶H仍然敏感，很可能具有Glu1-3Man9GlcNAc2结构。衣霉素是一种抗生素，它能抑制糖蛋白中N-连接的寡糖单元的加成，对这些蛋白质的分泌也有类似的不同作用。高尔基酶α-甘露糖苷酶II的抑制剂苦马豆素对蛋白质的分泌速度没有影响，尽管在这种情况下蛋白质是以一种异常的N-连接的、部分复杂的寡糖分泌的。α1-抗胰蛋白酶和α1-抗糜蛋白酶从粗面内质网到高尔基体的运动显然需要N-连接的低聚糖至少加工成Man9GlcNAc2形式；这种低聚糖可能形成某些分泌蛋白的运输受体识别位置的一部分。
1-Deoxynojirimycin is a specific inhibitor of glucosidases I and II, the 1st enzymes that process N-linked oligosaccharides after their transfer to polypeptides in the rough endoplasmic reticulum. In a pulse-chase experiment, 1-deoxynojirimycin greatly reduced the rate of secretion of .alpha.1-antitrypsin and .alpha.1-antichymotrypsin by human hepatoma HepG2 cells, but had marginal effects on secretion of the glycoproteins C3 and transferrin, or of albumin. As judged by equilibrium gradient centrifugation, 1-deoxynojirimycin caused .alpha.1-antitrypsin and .alpha.1-antichymotrypsin to accumulate in the rough endoplasmic reticulum. The oligosaccharides on cell-associated .alpha.1-antitrypsin and .alpha.1-antichymotrypsin synthesized in the presence of 1-deoxynojirimycin, remained sensitive to endoglycosidase H and most likely had the structure Glu1-3Man9GlcNAc2. Tunicamycin, an antibiotic that inhibits addition of N-linked oligosaccharide units to glycoproteins, had a similar differential effect on secretion of these proteins. Swainsonine, an inhibitor of the Golgi enzyme .alpha.-mannosidase II, had no effect on the rates of protein secretion, although the proteins were in this case secreted with an abnormal N-linked, partially complex, oligosaccharide. The movement of .alpha.1-antitrypsin and .alpha.1-antichymotrypsin from the rough endoplasmic reticulum to the Golgi evidently requires that the N-linked oligosaccharides be processed to at least the Man9GlcNAc2 form; this oligosaccharide possibly forms part of the recognition site of a transport receptor for certain secretory proteins.