Receptor-associated protein facilitates proper folding and maturation of the low-density lipoprotein receptor and its class 2 mutants.
Receptor-associated protein facilitates proper folding and maturation of the low-density lipoprotein receptor and its class 2 mutants.
复制标题
受体相关蛋白促进低密度脂蛋白受体及其 2 类突变体的正确折叠和成熟。
DOI：
10.1021/bi011894i
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发表时间：
2002
期刊：
影响因子：
2.9
通讯作者：
Bu,Guojun
中科院分区：
文献类型：
--
作者：
Li,Yonghe;Lu,Wenyan;Schwartz,AlanL;Bu,Guojun
家族性高胆固醇血症是低密度脂蛋白受体（LDLR）各种突变的结果。在目前的研究中，我们发现一种特殊的分子伴侣，受体相关蛋白（RAP），促进野生型LDLR及其几个2类突变体的适当折叠和随后的胞外运输。与抗RAP抗体共免疫沉淀表明RAP与LDLR相互作用。在没有RAP共表达或存在RAP共表达的情况下，LDLR翻译后折叠和成熟的动力学分析表明RAP阻止了LDLR的聚集并促进了LDLR的成熟。此外，完整细胞中Ca2+的消耗会损害LDLR折叠，RAP的共表达部分纠正了这种错误折叠。最后，我们发现在RAP共表达的情况下，成熟细胞表面LDLR的增加在其内吞和降解125i - ldl的能力方面具有功能。综上所述，我们的研究结果表明RAP促进了LDLR及其2类突变体的折叠、转运和成熟。
Familial hypercholesterolemia is the consequence of various mutations in the low-density lipoprotein receptor (LDLR). In the current study, we show that a specialized molecular chaperone, the receptor-associated protein (RAP), promotes proper folding and subsequent exocytic trafficking of the wild-type LDLR and several of its class 2 mutants. Co-immunoprecipitation with anti-RAP antibody demonstrates that RAP interacts with the LDLR. Kinetic analyses of LDLR posttranslational folding and maturation in the absence or presence of RAP coexpression show that RAP prevents aggregation and promotes the maturation of the LDLR. Additionally, depletion of Ca2+in intact cells impairs LDLR folding, and coexpression of RAP partially corrects this misfolding. Finally, we show that the increased mature cell surface LDLR in the presence of RAP coexpression is functional in its ability to endocytose and degrade125I-LDL. Taken together, our results show that the folding, trafficking, and maturation of the LDLR and its class 2 mutants are promoted by RAP.