MAINTENANCE AND CONSEQUENCES OF MEMBRANE PHOSPHOLIPID ASYMMETRY

The outer monolayer of animal plasma membranes is principally composed of choline-phospholipids while the amino-phospholipids reside in the inner monolayer. This anisotropic distribution is a steady state. The choline-lipids are submitted to a slow and passive transmembrane diffu sion and the amino-lipids are inwardly transported by an ATP-dependent carrier, the amino-phospholipid translocase or 'flippase'. The transp ort system has been characterized functionally and recently associated in red cells with a 110-kDa Mg-ATPase. Experiments indicate that the translocase can maintain by itself the amino-lipid asymmetry without r equiring the help of cytoskeletal proteins. In the endoplasmic reticul um, phospholipids experience a facilitated diffusion involving a non-A TP-dependent 'flippase'. A similar system exists in the liver canalicu lar plasma membrane. It has been demonstrated that the phosphatidylcho line secretion into the bile is under the control of the P-glycoprotei n encoded by the mdr2 gene. The question arises whether the related pr otein from the mdr1 gene, which confers the multi-drug resistance to c ells in which it is expressed, could also function as a lipid flippase . In response to some cellular events, such as blood platelet stimulat ion, the phospholipid asymmetry may suddenly collapse. The exact mecha nism by which this randomization occurs is still unknown, but both a ' scramblase' protein and a minor lipid (PIP2) have been proposed as med iators of the event. Maintaining a plasma membrane asymmetry, even at the expense of energy consumption, is important for some cells: the ap pearance of phosphatidylserine into the outer membrane leaflet of bloo d cells generates a procoagulant surface catalysing the clot formation . It is also responsible for the recognition and phagocytosis of eryth rocytes by macrophages. Finally, the amino-phospholipid translocase co uld play an important role in the control of membrane curvature, parti cularly in the initiation of vesicle formation.