Lipid translocation across the plasma membrane of mammalian cells

The plasma membrane, which forms the physical barrier between the intra- an d extracellular milieu, plays a pivotal role in the communication of cells with their environment. Exchanging metabolites, transferring signals and pr oviding a platform for the assembly of multi-protein complexes are a few of the major functions of the plasma membrane, each of which requires partici pation of specific membrane proteins and/or lipids. It is therefore not sur prising that the two leaflets of the membrane bilayer each have their speci fic lipid composition. Although membrane lipid asymmetry has been known for many years, the mechanisms for maintaining or regulating the transbilayer lipid distribution are still not completely understood. Three major players have been presented over the past years: (1) an inward-directed pump speci fic for phosphatidylserine and phosphatidylethanolamine? known as aminophos pholipid translocase; (2) an outward-directed pump referred to as 'floppase ' with little selectivity for the polar headgroup of the phospholipid, but whose actual participation in transport of endogenous lipids has not been w ell established; and (3) a lipid scramblase, which facilitates bi-direction al migration across the bilayer of all phospholipid classes, independent of the polar headgroup. Whereas a concerted action of aminophospholipid trans locase and floppase could, in principle, account for the maintenance of lip id asymmetry in quiescent cells, activation of the scramblase and concomita nt inhibition of the aminophospholipid translocase causes a collapse of lip id asymmetry, manifested by exposure of phosphatidylserine on the cell surf ace. In this article, each of these transporters will be discussed, and the ir physiological importance will be illustrated by the Scott syndrome, a bl eeding disorder caused by impaired lipid scrambling. Finally, phosphatidyls erine exposure during apoptosis will be briefly discussed in relation to in hibition of translocase and simultaneous activation of scramblase. (C) 1999 Elsevier Science B.V. All rights reserved.