The human multidrug resistance protein MRP1 translocates sphingolipid analogs across the plasma membrane.
The human multidrug resistance protein MRP1 translocates sphingolipid analogs across the plasma membrane.
复制标题
人类多药耐药蛋白 MRP1 使鞘脂类似物穿过质膜。
作者：
R. Raggers;A. Helvoort;R. Evers;G. Meer
最近，我们提供的证据表明，ABC转运MDR 1 P-糖蛋白易位类似物的各种脂质类跨极化LLC-PK 1细胞的顶端质膜MDR 1 cDNA转染。在这里，我们表明，表达的基底外侧ABC转运蛋白MRP 1（多药耐药蛋白）诱导脂质运输到外质小叶的基底外侧质膜的LLC-PK 1细胞在15 degreesC。C6-NBD-葡萄糖神经酰胺合成的高尔基体复合体的胞质侧，但不是C6-NBD-鞘磷脂合成的高尔基体腔中，成为访问消耗BSA在基础培养基中。这表明不存在囊泡运输和C6-NBD-葡萄糖神经酰胺通过MRP 1穿过基底外侧膜的直接易位。与此相一致，脂质转运到细胞外质小叶依赖于细胞内谷胱甘肽浓度，并受到MRP 1抑制剂亚磺酰脲和吲哚美辛的抑制，但不受MDR 1 P-糖蛋白抑制剂PSC 833的抑制。与MDR 1 P-糖蛋白的广泛底物特异性相反，MRP 1选择性转运C6-NBD-葡萄糖神经酰胺和C6-NBD-鞘磷脂，后者仅当其通过布雷菲德菌素A从高尔基体腔释放时。这显示了脂质易位的特殊性质。我们的结论是，MDR 1的P-糖蛋白和MRP 1的转运活性必须考虑到在脂质的运输到细胞表面的研究。
Recently, we have provided evidence that the ABC-transporter MDR1 P-glycoprotein translocates analogs of various lipid classes across the apical plasma membrane of polarized LLC-PK1 cells transfected with MDR1 cDNA. Here, we show that expression of the basolateral ABC-transporter MRP1 (the multidrug resistance protein) induced lipid transport to the exoplasmic leaflet of the basolateral plasma membrane of LLC-PK1 cells at 15 degreesC. C6-NBD-glucosylceramide synthesized on the cytosolic side of the Golgi complex, but not C6-NBD-sphingomyelin synthesized in the Golgi lumen, became accessible to depletion by BSA in the basal culture medium. This suggests the absence of vesicular traffic and direct translocation of C6-NBD-glucosylceramide by MRP1 across the basolateral membrane. In line with this, transport of the lipid to the exoplasmic leaflet depended on the intracellular glutathione concentration and was inhibited by the MRP1-inhibitors sulfinpyrazone and indomethacin, but not by the MDR1 P-glycoprotein inhibitor PSC 833. In contrast to the broad substrate specificity of the MDR1 P-glycoprotein, MRP1 selectively transported C6-NBD-glucosylceramide and C6-NBD-sphingomyelin, the latter only when it was released from the Golgi lumen by brefeldin A. This shows the specific nature of the lipid translocation. We conclude that the transport activity of MDR1 P-glycoprotein and MRP1 must be taken into account in studies on the transport of lipids to the cell surface.
影响因子：
11.2
作者：
A. Lorico;G. Rappa;R. A. Finch;Di Yang;R. A. Flavell;Alan C. Sartorelli
通讯作者：
A. Lorico;G. Rappa;R. A. Finch;Di Yang;R. A. Flavell;Alan C. Sartorelli
影响因子：
11.2
作者：
G. Rappa;A. Lorico;R. Flavell;A. Sartorelli
通讯作者：
G. Rappa;A. Lorico;R. Flavell;A. Sartorelli
DOI：
10.1073/pnas.86.2.695
发表时间：
1989-01-01
影响因子：
11.1
作者：
CORDONCARDO, C;OBRIEN, JP;BERTINO, JR
通讯作者：
BERTINO, JR