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Journal of Lipid Research, Vol. 44, 233-242, February 2003
Copyright © 2003 by Lipid Research, Inc.
Thematic Review |
Regulation of transbilayer plasma membrane phospholipid asymmetry
Medical Sciences Program, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Bloomington, IN 47405
1 To whom correspondence should be addressed. e-mail: daleked{at}indiana.edu
Lipids in biological membranes are asymmetrically distributed across the bilayer; the amine-containing phospholipids are enriched on the cytoplasmic surface of the plasma membrane, while the choline-containing and sphingolipids are enriched on the outer surface. The maintenance of transbilayer lipid asymmetry is essential for normal membrane function, and disruption of this asymmetry is associated with cell activation or pathologic conditions. Lipid asymmetry is generated primarily by selective synthesis of lipids on one side of the membrane. Because passive lipid transbilayer diffusion is slow, a number of proteins have evolved to either dissipate or maintain this lipid gradient. These proteins fall into three classes: 1) cytofacially-directed, ATP-dependent transporters ("flippases"); 2) exofacially-directed, ATP-dependent transporters ("floppases"); and 3) bidirectional, ATP-independent transporters ("scramblases"). The flippase is highly selective for phosphatidylserine and functions to keep this lipid sequestered from the cell surface. Floppase activity has been associated with the ABC class of transmembrane transporters. Although they are primarily nonspecific, at least two members of this class display selectivity for their substrate lipid. Scramblases are inherently nonspecific and function to randomize the distribution of newly synthesized lipids in the endoplasmic reticulum or plasma membrane lipids in activated cells.
It is the combined action of these proteins and the physical properties of the membrane bilayer that generate and maintain transbilayer lipid asymmetry.
Abbreviations: flippases, ATP-dependent transporters; floppases, ATP-dependent transporters; Glc-Cer, glucosylceramide; NBD, 7-nitrobenz-2-oxa-1,3-diazol-4-yl; PA, phosphatidic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PI, phosphatidylinositol; PIP, phosphatidylinositol-4-monophosphate; PIP2, phosphatidylinositol-4,5-bisphosphate; PS, phosphatidylserine; scramblases, ATP-independent transporters; SM, sphingomyelin
Supplementary key words flippase • floppase • scramblase • phosphatidylserine
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