Somatic Cell Genetic Mutants with Altered Cholesterol Metabolism and Altered Endocytosis of Low Density Lipoprotein

* 低密度脂蛋白（LDL）的细胞摄取通过受体介导的内吞作用介导。常见的高胆固醇血症与许多突变密切相关，这些突变扭曲了LDL受体的转运和加工。为了了解与受体介导的LDL内吞作用相关的固醇代谢的病理变化，具有改变的固醇代谢的体细胞突变体可能是有价值的。特别是，我们试图提出这样的体细胞突变体作为模型细胞异常固醇代谢疾病。在这项研究中，我们研究了三种不同的突变体与改变受体介导的途径LDL。1。中国仓鼠卵巢（CHO）细胞的莫能菌素抗性突变体在LDL与细胞表面受体的结合上有缺陷。该突变体在LDL存在下比CHO细胞表现出更高的甾醇合成，并且在突变体中观察到LDL受体的缺陷性下调。在突变体中，与LDL受体相关的N-和O-连接寡糖的N-连接糖基化似乎发生了改变，这表明高尔基体的功能发生了改变.小鼠Balb/3 T3细胞的莫能菌素抗性突变体在LDL的内吞方面存在缺陷。该突变体还表现出对高尔基体功能的不良下调，似乎引起膜组分的变化，这可能影响LDL的内吞作用.中国仓鼠V79细胞的Compactin抗性突变体在LDL受体以及LDL的内吞作用方面存在缺陷。突变体合成的LDL受体分子具有异常的O-糖基化，其转换速度比野生型快得多，表明缺乏O-糖基的LDL受体分子对蛋白酶作用敏感。

* Cellular uptake of low density lipoprotein (LDL) is mediated through receptor mediated endocytosis. Familiar hypercholesterolemia is closely linked to a number of mutations which distort the transport and processing of LDL receptors. To understand pathological changes in sterol metabolism in relation to receptor-mediated endocytosis of LDL, somatic cell mutants with altered sterol metabolism could be valuable. In particular, we try to propose such somatic cell mutants as model cell for abnormal sterol metabolic diseases. In this study we have studied three different mutants with altered receptor-mediated pathway of LDL.1. Monensin-resistant mutant of Chinese hamster overy (CHO) cells was defective in LDL binding to the cell surface receptor. This mutant showed higher sterol synthesis in the presence of LDL than CHO cells, and defective down-regulation of LDL receptors was observed in the mutant. N-linked glycosylation appeared to be altered among N- and O- linked oligosaccharides associated with LDL receptors in the mutant, suggesting altered function of Golgi apparatus.2. Monensin-resistant mutant of mouse Balb/3T3 cells was defective in endocytosis of LDL. This mutant also showed poor down-regulation of function of Golgi function appears to cause change(s) of membranous component, which may affect the endocytosis of LDL.3. Compactin-resistant mutant of Chinese hamster V79 cells was defective in LDL-receptor as well as endocytosis of LDL. LDL receptor synthesized in the mutant showed truncated molecules with aberrant O-linked sugar glycosylation.The turnover of mutant LDL receptors was much faster than that of wild ones, suggesting that the receptor molecules lacking O-linked sugars is sensitive to protease action.