Functional reconstitution of human FcRn in Madin-Darby canine kidney cells requires co-expressed human β2-microglobulin
Functional reconstitution of human FcRn in Madin-Darby canine kidney cells requires co-expressed human β2-microglobulin
复制标题
DOI：
10.1074/jbc.m202367200
复制
发表时间：
2002-08-02
影响因子：
4.8
通讯作者：
Blumberg, RS
中科院分区：
文献类型：
--
作者：
Claypool, SM;Dickinson, BL;Blumberg, RS
主要的组织相容性复合体i类相关的新生儿Fc受体FcRn以异源二聚体的形式组装，由重链和β(2)-微球蛋白（β (2)m）组成，这对FcRn的功能至关重要。我们观察到，在Madin-Darby犬肾（MDCK）细胞中，人FCRn介导IgG双向转运的功能在人β (2)m亚型共表达后显著增强。在MDCK细胞中，人β (2)m的存在赋予人FcRn在稳定状态下退出内质网并获得成熟碳水化合物侧链修饰的能力增强，成熟的动力学更快，并且增强了作为能够结合IgG的成熟糖蛋白在细胞表面的定位。虽然未成熟碳水化合物侧链修饰的人FcRn能够表现出ph依赖性的IgG结合，但只有成熟碳水化合物侧链修饰的人FcRn在细胞表面被检测到。这些结果表明，人FcRn通过正常的分泌途径到达细胞表面，人FcRn在MDCK细胞中的适当表达和功能取决于人β (2)m的共表达。
The major histocompatibility complex class I-related neonatal Fc receptor, FcRn, assembles as a heterodimer consisting of a heavy chain and beta(2)-microglobulin (beta(2)m), which is essential for FcRn function. We observed that, in Madin-Darby canine kidney (MDCK) cells, the function of human FCRn in mediating the bidirectional transport of IgG was significantly increased upon coexpression of the human isoform of beta(2)m. In MDCK cells, the presence of human beta(2)m endowed upon human FcRn an enhanced ability to exit the endoplasmic reticulum and acquire mature carbohydrate side-chain modifications at steady state, a faster kinetics of maturation, and augmented localization at the cell surface as a mature glycoprotein able to bind IgG. Although human FcRn with immature carbohydrate side-chain modifications was capable of exhibiting pH-dependent binding of IgG, only human FcRn with mature carbohydrate side-chain modifications was detected on the cell surface. These results show that human FcRn travels to the cell surface via the normal secretory pathway and that the appropriate expression and function of human FCRn in MDCK cells depends upon the co-expression of human beta(2)m.