Ezrin regulates the expression of Mrp2/Abcc2 and Mdr1/Abcb1 along the rat small intestinal tract

被引:18
|
作者
Nakano, Takafumi [1 ]
Sekine, Shuichi [1 ]
Ito, Kousei [1 ]
Horie, Toshiharu [1 ]
机构
[1] Chiba Univ, Lab Biopharmaceut, Grad Sch Pharmaceut Sci, Chuo Ku, Chiba, Japan
关键词
ezrin; MDR1/ABCB1; MRP2/ABCC2; small intestinal tract; PROTEIN-KINASE-C; FOOD-DERIVED CARCINOGEN; ERM-FAMILY PROTEINS; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; STRUCTURAL BASIS; EFFLUX PROTEINS; TRANSPORT; MRP2; PHOSPHORYLATION;
D O I
10.1152/ajpgi.00187.2013
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Multidrug resistance-associated protein 2 (MRP2)/ATP-binding cassette protein C2 (ABCC2) and multidrug resistance protein 1 (MDR1)/ABCB1 are well-known efflux transporters located on the brush border membrane of the small intestinal epithelia, where they limit the absorption of a broad range of substrates. The expression patterns of MRP2/ABCC2 and MDR1/ABCB1 along the small intestinal tract are tightly regulated. Several reports have demonstrated the participation of ERM (ezrin/radixin/moesin) proteins in the posttranslational modulation of MRP2/ABCC2 and MDR1/ABCB1, especially with regard to their membrane localization. The present study focused on the in vivo expression profiles of MRP2/ABCC2, MDR1/ABCB1, ezrin, and phosphorylated ezrin to further elucidate the relationship between the efflux transporters and the ERM proteins. The current results showed good correlation between the phosphorylation status of ezrin and Mrp2/Abcc2 expression along the gastrointestinal tract of rats and between the expression profiles of both ezrin and Mdr1/Abcb1 in the small intestine. We also demonstrated the involvement of conventional protein kinase C isoforms in the regulation of ezrin phosphorylation. Furthermore, experiments conducted with wild-type (WT) ezrin and a T567A (Ala substituted Thr) dephosphorylated mutant showed a decrease in membrane surface-localized and total expressed MRP2/ABCC2 in T567A-expressing vs. WT ezrin-expressing Caco-2 cells. In contrast, T567A- and WT-expressing cells both showed an increase in membrane surface-localized and total expressed MDR1/ABCB1. These findings suggest that the phosphorylation status and the expression profile of ezrin differentially direct MRP2/ABCC2 and MDR1/ABCB1 expression, respectively, along the small intestinal tract.
引用
收藏
页码:G807 / G817
页数:11
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