Three types of low density lipoprotein receptor-deficient mutant have pleiotropic defects in the synthesis of N-linked, O-linked, and lipid-linked carbohydrate chains.
Three types of low density lipoprotein receptor-deficient mutant have pleiotropic defects in the synthesis of N-linked, O-linked, and lipid-linked carbohydrate chains.
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三种类型的低密度脂蛋白受体缺陷突变体在合成N连接，O连接和脂质连接的碳水化合物链中具有多效性缺陷。
DOI：
10.1083/jcb.102.5.1576
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发表时间：
1986-05
期刊：
影响因子：
--
通讯作者：
Krieger M
中科院分区：
文献类型：
--
作者：
Kingsley DM;Kozarsky KF;Segal M;Krieger M
应用生物化学、免疫学和遗传学技术研究了三种低密度脂蛋白（LDL）受体缺陷仓鼠细胞的遗传缺陷。先前分离的ldlB、ldlC和ldlD突变体都合成了基本正常量的LDL受体的125，000-D前体形式，但不能将该受体加工成155，000-D的成熟形式。相反，这些突变体产生异常小的异质受体，到达细胞表面，但随后迅速降解。这些细胞中LDL受体的异常大小是由于LDL受体的N-和O-连接的碳水化合物链的加工缺陷。这些细胞中的加工缺陷似乎是普遍的，因为ldlB，ldlC和ldlD突变体也表现出有缺陷的病毒糖蛋白的糖基化，糖脂合成的改变，和几种毒性凝集素的抗性的变化。初步结构研究表明，这些细胞在负责糖脂合成的高尔基体相关加工反应的多个阶段以及糖蛋白的N-连接和O-连接碳水化合物链中存在缺陷。ldl突变体和大量先前分离的CHO糖基化缺陷突变体之间的比较表明，ldlB、ldlC和ldlD细胞中的遗传缺陷是独特的，并且只有非常特定类型的碳水化合物改变才能显著影响LDL受体功能。
Biochemical, immunological, and genetic techniques were used to investigate the genetic defects in three types of low density lipoprotein (LDL) receptor-deficient hamster cells. The previously isolated ldlB, ldlC, and ldlD mutants all synthesized essentially normal amounts of a 125,000-D precursor form of the LDL receptor, but were unable to process this receptor to the mature form of 155,000 D. Instead, these mutants produced abnormally small, heterogeneous receptors that reached the cell surface but were rapidly degraded thereafter. The abnormal sizes of the LDL receptors in these cells were due to defective processing of the LDL receptor's N- and O-linked carbohydrate chains. Processing defects in these cells appeared to be general since the ldlB, ldlC, and ldlD mutants also showed defective glycosylation of a viral glycoprotein, alterations in glycolipid synthesis, and changes in resistance to several toxic lectins. Preliminary structural studies suggested that these cells had defects in multiple stages of the Golgi-associated processing reactions responsible for synthesis of glycolipids and in the N-linked and O- linked carbohydrate chains of glycoproteins. Comparisons between the ldl mutants and a large number of previously isolated CHO glycosylation defective mutants showed that the genetic defects in ldlB, ldlC, and ldlD cells were unique and that only very specific types of carbohydrate alteration could dramatically affect LDL receptor function.
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影响因子：
7.8
作者：
ROBBINS, AR;PENG, SS;MARSHALL, JL
通讯作者：
MARSHALL, JL
影响因子：
64.5
作者：
KRIEGER, M
通讯作者：
KRIEGER, M
影响因子：
64.5
作者：
DUNPHY, WG;BRANDS, R;ROTHMAN, JE
通讯作者：
ROTHMAN, JE
影响因子：
64.5
作者：
KINGSLEY, DM;KOZARSKY, KF;KRIEGER, M
通讯作者：
KRIEGER, M
影响因子：
7.8
作者：
ROBBINS, AR;OLIVER, C;MELLMAN, I
通讯作者：
MELLMAN, I