GENETIC-EVIDENCE THAT THE STEROID-REGULATED TRAFFICKING OF CELL-SURFACE GLYCOPROTEINS IN RAT HEPATOMA-CELLS IS MEDIATED BY GLUCOCORTICOID-INDUCIBLE CELLULAR-COMPONENTS
GENETIC-EVIDENCE THAT THE STEROID-REGULATED TRAFFICKING OF CELL-SURFACE GLYCOPROTEINS IN RAT HEPATOMA-CELLS IS MEDIATED BY GLUCOCORTICOID-INDUCIBLE CELLULAR-COMPONENTS
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DOI：
10.1002/jcb.240350402
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发表时间：
1987-12-01
影响因子：
4
通讯作者：
COOK, PW
中科院分区：
文献类型：
--
作者：
FIRESTONE, GL;JOHN, NJ;COOK, PW
翻译后成熟和区室化反应的生物学控制在蛋白质运输到其最终细胞目的地期间对蛋白质起作用，对于正常细胞功能至关重要。利用小鼠乳腺肿瘤病毒（MMTV）糖蛋白的表达作为病毒感染的大鼠肝癌细胞系M1.54中的敏感探针，我们发现并记录了一种新型糖皮质激素调节的运输途径，该途径控制MMTV糖蛋白的细胞表面定位。M1.54细胞的一种补体选择性衍生物CR4在地塞米松存在下不能compatmentalize细胞表面MMTV糖蛋白。为了从遗传学上测试这种糖蛋白运输途径是否由细胞或病毒基因产物介导，将CR4细胞与感染的Fu5大鼠肝细胞融合。CR4 × CR4的间接免疫荧光Fu5异核体显示，Fu5仅在暴露于1 UmM地塞米松后才补充CR4中的缺陷。Fu5增殖的糖皮质激素抑制被利用来恢复受体缺陷的未感染的衍生物EDR3，其表达低100倍水平的[3H]地塞米松结合活性。分析CR4 ×EDR3细胞融合的间接免疫荧光显示，EDR3细胞补充CR4的地塞米松依赖性的方式，这表明EDR3提供了一个功能性的运输组件，而CR4提供了一个功能性的糖皮质激素受体的异核体。两者合计，我们的研究结果表明，细胞编码的糖皮质激素诱导成分介导的细胞表面MMTV糖蛋白的调节贩运。
The biological control of posttranslational maturation and compartmentalization reactions that operate upon proteins during transport to their final cellular destinations is crucial for normal cellular function. Using the expression of mouse mammary tumor virus (MMTV) glycoproteins as sensitive probe in the viral-infected rat hepatoma cell line M1.54, we have discovered and documented a novel glucocorticoid-regulated trafficking pathway that controls the cell surface localization of MMTV glycoprotiens. One complement-seleceted derivative of M1.54 cells, CR4, failed to compatmentalize cell surface MMTV glycoproteins in the presence of dexamethasone. To test genetically if this glycoprotein trafficking pathway is mediated by cellular or viral gene products, CR4 cells were fused with infected Fu5 rat hepatome cells. Indirect immunofluorescence of CR4 .times. Fu5 heterokaryons revealed that Fu5 complemented the defect inCR4 only after exposure to 1 UmM dexamethasone. The glucocorticoid inhibition of Fu5 proliferation was exploited to recover the receptor-deficient uninfected derivative EDR3 that expressed a 100-fold lower level of [3H]dexamethasone binding activity. Analysis of CR4 .times. EDR3 cell fusions by indirect immunofluorescence revealed that EDR3 cells complemented CR4 in a dexamethasone-dependent manner, suggesting that EDR3 supplied a functional trafficking component while CR4 provided a functional glucocorticoid receptor to the heterokaryons. Taken together, our results demonstrate that cellular-encoded glucocorticoid-inducible components mediate the regulated trafficking of cell surface MMTV glycoproteins.