The human MDR3 P‐glycoprotein promotes translocation of phosphatidylcholine through the plasma membrane of fibroblasts from transgenic mice

FEBS Letters

Smit, Jaap J.M.³  Timmermans-Hereijgers, Johanna L.P.M.¹  Roelofsen, Ben¹  Smith, Alexander J.³  van Blitterswijk, Wim J.²  Wirtz, Karel W.A.¹  Borst, Piet³  Schinkel, Alfred H.³ 

[1] Centre of Biomembranes and Lipid Enzymology, Department of Lipid Biochemistry, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands;Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands;Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands

关键词: MDR3;    P-glycoprotein;    Phosphatidylcholine;    Flippase;   

DOI  :  10.1016/0014-5793(94)01135-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The mouse mdr2 P-glycoprotein (P-gp) and its human MDR3 homologue are present in high concentrations in the canalicular membrane of hepatocytes. Mice lacking this protein are unable to secrete phosphatidylcholine (PC) into bile, suggesting that this P-gp is a PC translocator. We have tested this in fibroblasts from transgenic mice expressing the MDR3 gene under a vimentin promoter. Transgenic and control fibroblasts were incubated with [¹⁴C]choline to label PC. When the labeled cells were incubated with a PC transfer protein and acceptor liposomes, transfer of radioactive PC was enhanced in transgenic cells relative to the wild type controls. We conclude that the MDR3 P-glycoprotein is able to promote the transfer of PC from the inner to the outer leaflet of the plasma membrane, supporting the idea that this protein functions as a PC flippase.

【 授权许可】

Unknown