[HTML][HTML] MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine

A van Helvoort, AJ Smith, H Sprong, I Fritzsche… - Cell, 1996 - cell.com
A van Helvoort, AJ Smith, H Sprong, I Fritzsche, AH Schinkel, P Borst, G van Meer
Cell, 1996cell.com
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° 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 …
Abstract
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°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°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.
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