THE HUMAN MDR3 P-GLYCOPROTEIN PROMOTES TRANSLOCATION OF PHOSPHATIDYLCHOLINE THROUGH THE PLASMA-MEMBRANE OF FIBROBLASTS FROM TRANSGENIC MICE

The mouse mdr2 P-glycoprotein (P-gp) and its human MDR3 homologue are present in high concentrations in the canalicular membrane of hepatocy tes. Mice lacking this protein are unable to secrete phosphatidylcholi ne (PC) into bile, suggesting that this P-gp is a PC translocator. We have tested this in fibroblasts from transgenic mice expressing the MD R3 gene under a vimentin promoter. Transgenic and control fibroblasts were incubated with [C-14]choline to label PC, When the labeled cells were incubated with a PC transfer protein and acceptor liposomes, tran sfer of radioactive PC was enhanced in transgenic cells relative to th e 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 a s a PC flippase.