赤血球膜における脂質非対称分布の維持と破綻のメカニズム

赤血球Scramblase のCholesterol による活性調節

抄録

Phospholipids (PLs) in erythrocyte membranes are asymmetrically distributed in the bilayer; amino PLs such as PS and PE reside exclusively in the inner leaflet and the outer leaflet is thus enriched with neutral PLs such as PC and SM. The localization of PS and PE is principally maintained by an activity of ATP-dependent Flippase. However, the asymmetric distribution is abolished by PL scrambling at critical cellular events like cell senescence. A detailed mechanism of PL scrambling is yet to be understood. Phospholipid scramblase 1 (PLSCR1), a 37 kDa transmembrane protein, has been reported to be responsible for Ca²⁺-dependent, PL nonselective bidirectional movement between the outer and inner leaflets. Based on the fact that this protein is present in cholesterol-rich raft I examined the effect of cholesterol on scrambling activity. In the present symposium using human erythrocyte membranes and liposomes reconstituted with purified PLSCR1 or its transmembrane peptides I could show that (1) cholesterol removal from erythrocyte membranes resulted in PS exposure to the outer leaflet in Ca²⁺-independent manner and (2) presence of cholesterol in the reconstituted liposomes suppressed scrambling activity. These results strongly suggest that cholesterol inhibits scrambling activity of PLSCR1 in human erythrocytes.