The endoplasmic reticulum is the principal site of synthesis and initial incorporation of membrane lipids in eukaryotic cells1; the enzymes of glycerolipid biosynthesis are exclusively located on its cytoplasmic surface2. To maintain a phospholipid bilayer in this organelle, newly synthesized phospholipids must be translocated to the lumenal surface. Consistent with this are measurements indicating that movement of phospholipids across microsomal membranes is rapid, with a half-time less than 5 min (refs 3 and 4). Rapid movement of phospholipids has also been detected across the plasma membrane of Bacillus megaterium5,6, another site of de novo lipid biosynthesis. The rapid transmembrane movement of phosphatidylcholine has not been detected, however, in vesicles prepared from microsomal lipids4. These latter data suggest involvement in the endoplasmic reticulum of a phospholipid-trans-locating protein, as was first proposed by Bretscher 7 who called it 'flippase9. Here we report reconstitution of a phospholipid flippase from rat liver microsomes into lipid vesicles.
ASJC Scopus subject areas