LIPOPROTEIN BINDING AND ENDOSOMAL ITINERARY OF THE LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN IN RAT-LIVER
LIPOPROTEIN BINDING AND ENDOSOMAL ITINERARY OF THE LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN IN RAT-LIVER
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DOI：
10.1073/pnas.86.23.9318
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发表时间：
1989-12-01
影响因子：
11.1
通讯作者：
HAVEL, RJ
中科院分区：
文献类型：
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作者：
LUND, H;TAKAHASHI, K;HAVEL, RJ
利用45 Ca与低密度脂蛋白受体（LDL-R）和LDL-R相关蛋白（LRP）结合的高亲和力来研究这两种蛋白在大鼠肝脏中的亚细胞分布。与LDL-R一样，LRP在大鼠肝内体膜中富集许多倍，在早期和晚期内体隔室中的相对分布与内体和细胞表面之间的再循环一致。肝内体膜中的高浓度LRP极大地促进了配体印迹中载脂蛋白E和B的脂蛋白的Ca依赖性结合的证明。LRP在肝实质细胞中的丰度是LDL-R的数倍，在肝内体中表现出广泛的降解，并在高尔基体和内质网中发现高浓度。这些数据表明LRP的高合成率似乎不受雌二醇处理大鼠的影响。在LRP的配体结合结构域中发现的重复的富含半胱氨酸的A基序似乎负责LRP、LDL-R和补体因子C9的Ca结合，并解释了这些蛋白质之间的免疫交叉反应性。较弱的配体印迹特性和对蛋白水解的异常敏感性最有可能导致在脂蛋白受体的常规测定中检测LRP的困难。我们的数据表明，这种蛋白质的广泛的蛋白水解加工，并与LRP在脂蛋白代谢中的功能作用是一致的。
The high affinity of 45Ca binding to the low density lipoprotein receptor (LDL-R) and the LDL-R-related protein (LRP) was utilized to study the subcellular distribution of these two proteins in rat liver. Like the LDL-R, LRP was manyfold enriched in rat liver endosomal membranes with a relative distribution in early and late endosomal compartments consistent with recycling between endosomes and the cell surface. The high concentration of LRP in hepatic endosomal membranes greatly facilitated demonstration of Ca-dependent binding of apolipoprotein E- and B-containing lipoproteins in ligand blots. LRP was severalfold more abundant than the LDL-R in hepatic parenchymal cells, showed extensive degradation in hepatic endosomes, and was found in high concentrations in the Golgi apparatus and endoplasmic reticulum. These data suggest a high rate of synthesis of LRP that appeared to be unaffected by treatment of rats with estradiol. The repeating cysteine-rich A-motif found in the ligand-binding domain of LRP appeared to be responsible for Ca binding by LRP, LDL-R, and complement factor C9 and accounted for immunological cross-reactivity among these proteins. Weaker ligand-blotting properties and an extraordinary susceptibility to proteolysis most likely contribute to the difficulty of detecting LRP in conventional assays for lipoprotein receptors. Our data suggest an extensive proteolytic processing of this protein and are consistent with a functional role of LRP in lipoprotein metabolism.