MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine.
The human MDR1 P-glycoprotein (Pgp) extrudes a variety of drugs across the plasma membrane. The homologous MDR3 Pgp is required for phosphatidylcholine secretion into bile. After stable transfection of epithelial LLC-PK1 cells, MDR1 and MDR3 Pgp were localized in the apical membrane. At 15 degrees C, newly synthesized short-chain analogs of various membrane lipids were recovered in the apical albumin-containing medium of MDR1 cells but not control cells. MDR inhibitors and energy depletion reduced apical release. MDR3 cells exclusively released a short-chain phosphatidylcholine. Since no vesicular secretion occurs at 15 degrees C, the short-chain lipids must have been translocated by the Pgps across the plasma membrane before extraction into the medium by the lipid-acceptor albumin.
Department of Cell Biology, Faculty of Medicine and Institute of Biomembranes, Universiteit Utrecht, The Netherlands.
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A
van Helvoort
A J
AJ
Smith
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H
Sprong
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I
Fritzsche
A H
AH
Schinkel
P
P
Borst
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G
van Meer
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002460:Cell Line; D016764:Cell Polarity; D004848:Epithelium; D006801:Humans; D007668:Kidney; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry / Q000145:classification; D051379:Mice; D010713:Phosphatidylcholines / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013379:Substrate Specificity; D013552:Swine; D014162:Transfection; D014700:Verapamil / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D008055:Lipids; D010713:Phosphatidylcholines; D011993:Recombinant Fusion Proteins; D014750:Vincristine; C095122:multidrug resistance protein 3; D014700:Verapamil