Band 3, an Accidental Flippase for Anionic Phospholipids?

The inward translocation of the monovalent anionic phospholipid 1-palmitoyl-sn-glycero-3-phosphomethanol in the membrane of human erythrocytes is a fast process (t/2 = 11 min, 37 degrees C). Translocation of the protonated uncharged phospholipid is not responsible for the fast flip rate, and mediation of translocation by the aminophospholipid flippase could be excluded. Involvement of the anion exchanger band 3 in this process was derived from its inhibition (40-70%) by several established inhibitors of band 3-mediated anion exchange and its acceleration after proteolysis of band 3 by external papain. The translocation of the dianionic NBD-labeled phosphatidic acid is 5-fold slower, but also affected by the inhibitors. Thus, the anion exchanger can act as a flippase, defined as a transporter accepting substrates from the lipid bilayer.