Lipid flippases and their biological functions

Cellular and Molecular Life Sciences

Volumn 63, Issue 24, 2006, Pages 2908-2921

  Pomorski, T ^a   Menon, A K ^b  

^a HUMBOLDT UNIVERSITY   (Germany)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

ABC transporter; Lipid flip flop; Membrane assembly; Membrane asymmetry; N glycosylation; P type ATPase; Scramblase; Vesicle budding

Indexed keywords

ABC TRANSPORTER; ADENOSINE TRIPHOSPHATASE; FLIPPASE; GLYCEROPHOSPHOLIPID; LIPID; MEMBRANE LIPID; PHOSPHOLIPID; UNCLASSIFIED DRUG;

BIOSYNTHESIS; ENDOPLASMIC RETICULUM; ENERGY; ENZYME ACTIVITY; EUKARYOTE; EUKARYOTIC CELL; HUMAN; LIPID ANALYSIS; LIPID BILAYER; LIPID TRANSPORT; LIPID VESICLE; MEMBRANE BIOLOGY; MEMBRANE TRANSPORT; NONHUMAN; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; REVIEW;

ADENOSINE TRIPHOSPHATASES; ATP-BINDING CASSETTE TRANSPORTERS; BIOLOGICAL TRANSPORT, ACTIVE; ENDOPLASMIC RETICULUM; GLYCEROPHOSPHOLIPIDS; INTRACELLULAR MEMBRANES; LIPID METABOLISM; LIPIDS; MODELS, BIOLOGICAL; MODELS, MOLECULAR; PHOSPHOLIPID TRANSFER PROTEINS; TRANSPORT VESICLES;

BACTERIA (MICROORGANISMS); EUKARYOTA;

EID: 33846097207     PISSN: 1420682X     EISSN: 15691632     Source Type: Journal    
DOI: 10.1007/s00018-006-6167-7     Document Type: Review

References (178)

1. Voelker, D. R. (2005) Bridging gaps in phospholipid transport. Trends Biochem. Sci. 30, 396-404.
2. Holthuis, J. C. and Levine, T. P. (2005) Lipid traffic: floppy drives and a superhighway. Nat. Rev. Mol. Cell Biol. 6, 209-220.
3. Janssen, M. J., Koorengevel, M. C., de Kruijff, B. and de Kroon, A. I. (1999) Transbilayer movement of phosphatidylcholine in the mitochondrial outer membrane of Saccharomyces cerevisiae is rapid and bidirectional. Biochim. Biophys. Acta 1421, 64-76.
4. Nemoto, N., Shida, Y., Shimada, H., Oshima, T. and Yamagishi, A. (2003) Characterization of the precursor of tetraether lipid biosynthesis in the thermoacidophilic archaeon Thermoplasma acidophilum. Extremophiles 7, 235-243.
5. Kornberg, R. D. and McConnell, H. M. (1971) Inside-outside transitions of phospholipids in vesicle membranes. Biochemistry 10, 1111-1120.
6. John, K., Schreiber, S., Kubelt, J., Herrmann, A. and Muller, P. (2002) Transbilayer movement of phospholipids at the main phase transition of lipid membranes: implications for rapid flip-flop in biological membranes. Biophys. J. 83, 3315-3323.
7. Liu, J. and Conboy, J. C. (2005) 1,2-diacyl-phosphatidylcholine flip-flop measured directly by sum-frequency vibrational spectroscopy. Biophys. J. 89, 2522-2532.
8. Rothman, J. E. and Dawidowicz, E. A. (1975) Asymmetric exchange of vesicle phospholipids catalyzed by the phosphatidylcholine exhange protein. Measurement of inside-outside transitions. Biochemistry 14, 2809-2816.
9. Lenard, J. and Rothman, J. E. (1976) Transbilayer distribution and movement of cholesterol and phospholipid in the membrane of influenza virus. Proc. Natl. Acad. Sci. USA 73, 391-395.
10. Seigneuret, M. and Devaux, P. F. (1984) ATP-dependent asymmetric distribution of spin-labeled phospholipids in the erythrocyte membrane: relation to shape changes. Proc Natl Acad Sci USA 81, 3751-3755.
11. Zilversmit, D. B. and Hughes, M. E. (1977) Extensive exchange of rat liver microsomal phospholipids. Biochim. Biophys. Acta 469, 99-110.
12. Buton, X., Morrot, G., Fellmann, P. and Seigneuret, M. (1996) Ultrafast glycerophospholipid-selective transbilayer motion mediated by a protein in the endoplasmic reticulum membrane. J. Biol. Chem. 271, 6651-6657.
13. Marx, U., Lassmann, G., Holzhutter, H. G., Wustner, D., Muller, P., Hohlig, A., Kubelt, J. and Herrmann, A. (2000) Rapid flip-flop of phospholipids in endoplasmic reticulum membranes studied by a stopped-flow approach. Biophys. J. 78, 2628-2640.
14. Hrafnsdottir, S., Nichols, J. W. and Menon, A. K. (1997) Transbilayer movement of fluorescent phospholipids in Bacillus megaterium membrane vesicles. Biochemistry 36, 4969-4978.
15. Kubelt, J., Menon, A. K., Muller, P. and Herrmann, A. (2002) Transbilayer movement of fluorescent phospholipid analogues in the cytoplasmic membrane of Escherichia coli. Biochemistry 41, 5605-1562.
16. Vishwakarma, R. A., Vehring, S., Mehta, A., Sinha, A., Pomorski, T., Herrmann, A. and Menon, A. K. (2005) New fluorescent probes reveal that flippase-mediated flip-flop of phosphatidylinositol across the endoplasmic reticulum membrane does not depend on the stereochemistry of the lipid. Org. Biomol. Chem. 3, 1275-1283.
17. Noordam, P. C., van Echteld, C. J., de Kruijff, B., Verkleij, A. J. and de Gier, J. (1980) Barrier characteristics of membrane model systems containing unsaturated phosphatidylethanolamines. Chem. Phys. Lipids 27, 221-232.
18. van Duijn, G., Valtersson, C., Chojnacki, T., Verkleij, A. J., Dallner, G. and de Kruijff, B. (1986) Dolichyl phosphate induces non-bilayer structures, vesicle fusion and transbilayer movement of lipids: a model membrane study. Biochim. Biophys. Acta 861, 211-223.
19. De Kruijff, B. and Van Zoelen, E. J. (1978) Effect of the phase transition on the transbilayer movement of dimyristoyl phosphatidylcholine in unilamellar vesicles. Biochim. Biophys. Acta 511, 105-115.
20. Kol, M. A., de Kroon, A. I., Rijkers, D. T., Killian, J. A. and de Kruijff, B. (2001) Membrane-spanning peptides induce phospholipid flop: a model for phospholipid translocation across the inner membrane of E. coli. Biochemistry 40, 10500-10506.
21. Kol, M. A., van Laak, A. N., Rijkers, D. T., Killian, J. A., de Kroon, A. I. and de Kruijff, B. (2003) Phospholipid flop induced by transmembrane peptides in model membranes is modulated by lipid composition. Biochemistry 42, 231-237.
22. Kol, M. A., van Dalen, A., de Kroon, A. I. and de Kruijff, B. (2003) Translocation of phospholipids is facilitated by a subset of membrane-spanning proteins of the bacterial cytoplasmic membrane. J. Biol. Chem. 278, 24586-24593.
23. Hope, M. J. and Cullis, P. R. (1987) Lipid asymmetry induced by transmembrane pH gradients in large unilamellar vesicles. J. Biol. Chem. 262, 4360-4366.
24. Hope, M. J., Redelmeier, T. E., Wong, K. F., Rodrigueza, W. and Cullis, P. R. (1989) Phospholipid asymmetry in large unilamellar vesicles induced by transmembrane pH gradients. Biochemistry 28, 4181-4187.
25. Redelmeier, T. E., Hope, M. J. and Cullis, P. R. (1990) On the mechanism of transbilayer transport of phosphatidylglycerol in response to transmembrane pH gradients. Biochemistry 29, 3046-3053.
26. Eastman, S. J., Hope, M. J. and Cullis, P. R. (1991) Transbilayer transport of phosphatidic acid in response to transmembrane pH gradients. Biochemistry 30, 1740-1745.
27. Boon, J. M. and Smith, B. D. (2001) Facilitated phosphatidylcholine flip-flop across erythrocyte membranes using low molecular weight synthetic translocases. J. Am. Chem. Soc. 123, 6221-6226.
28. Boon, J. M., Lambert, T. N., Smith, B. D., Beatty, A. M., Ugrinova, V. and Brown, S. N. (2002) Structure/activity study of tris(2-aminoethyl)amine- derived translocases for phosphatidylcholine. J. Org. Chem. 67, 2168-2174.
29. Boon, J. M., Lambert, T. N., Sisson, A. L., Davis, A. P. and Smith, B. D. (2003) Facilitated phosphatidylserine (PS) flip-flop and thrombin activation using a synthetic PS scramblase. J. Am. Chem. Soc. 125, 8195-8201.
30. Bishop, W. R. and Bell, R. M. (1985) Assembly of the endoplasmic reticulum phospholipid bilayer: the phosphatidylcholine transporter. Cell 42, 51-60.
31. Herrmann, A., Zachowski, A. and Devaux, P. F. (1990) Protein-mediated phospholipid translocation in the endoplasmic reticulum with a low lipid specificity. Biochemistry 29, 2023-2027.
32. Huijbregts, R. P., de Kroon, A. I. and de Kruijff, B. (1998) Rapid transmembrane movement of newly synthesized phosphatidylethanolamine across the inner membrane of Esch erichia coli. J. Biol. Chem. 273, 18936-18942.
33. Backer, J. M. and Dawidowicz, E. A. (1987) Reconstitution of a phospholipid flippase from rat liver microsomes. Nature 327, 341-343.
34. Rothman, J. E. and Kennedy, E. P. (1977) Rapid transmembrane movement of newly synthesized phospholipids during membrane assembly. Proc. Natl. Acad. Sci. USA 74, 1821-1825.
35. Menon, A. K., Watkins, W. E. and Hrafnsdottir, S. (2000) Specific proteins are required to translocate phosphatidylcholine bidirectionally across the endoplasmic reticulum. Curr. Biol. 10, 241-252.
36. Nicolson, T. and Mayinger, P. (2000) Reconstitution of yeast microsomal lipid flip-flop using endogenous aminophospholipids. FEBS Lett. 476, 277-281.
37. Hrafnsdottir, S. and Menon, A. K. (2000) Reconstitution and partial characterization of phospholipid flippase activity from detergent extracts of the Bacillus subtilis cell membrane. J. Bacteriol. 182, 4198-4206.
38. Watkins, W. E. and Menon, A. K. (2002) Reconstitution of phospholipid flippase activity from, E. coli inner membrane: a test of the protein translocon as a candidate flippase. Biol. Chem. 383, 1435-1440.
39. Gummadi, S. N. and Menon, A. K. (2002) Transbilayer movement of dipalmitoylphosphatidylcholine in proteoliposomes reconstituted from detergent extracts of endoplasmic reticulum. Kinetics of transbilayer transport mediated by a single flippase and identification of protein fractions enriched in flippase activity. J. Biol. Chem. 277, 25337-25343.
40. Chang, Q. L., Gummadi, S. N. and Menon, A. K. (2004) Chemical modification identifies two populations of glycerophospholipid flippase in rat liver ER. Biochemistry 43, 10710-10718.
41. Rothman, J. E. and Lenard, J. (1977) Membrane asymmetry. Science 195, 743-753.
42. Zilversmit, D. B. (1978) Phospholipid-exchange proteins as membrane probes. Ann. NY Acad. Sci. 308, 149-163.
43. Langley, K. E. and Kennedy, E. P. (1979) Energetics of rapid transmembrane movement and of compositional asymmetry of phosphatidylethanolamine in membranes of Bacillus megaterium. Proc. Natl. Acad. Sci. USA 76, 6245-6249.
44. Kol, M. A., de Kroon, A. I., Killian, J. A. and de Kruijff, B. (2004) Transbilayer movement of phospholipids in biogenic membranes. Biochemistry 43, 2673-2681.
45. Rush, J. S. and Waechter, C. J. (1995) Transmembrane movement of a water-soluble analogue of mannosylphosphoryldolichol is mediated by an endoplasmic reticulum protein. J. Cell Biol. 130, 529-536.
46. Rush, J. S., van Leyen, K., Ouerfelli, O., Wolucka, B. and Waechter, C. J. (1998) Transbilayer movement of Glc-P-dolichol and its function as a glucosyl donor: protein-mediated transport of a water-soluble analog into sealed ER vesicles from pig brain. Glycobiology 8, 1195-1205.
47. Rush, J. S. and Waechter, C. J. (2004) Functional reconstitution into proteoliposomes and partial purification of a rat liver ER transport system for a water-soluble analogue of mannosylphosphoryldolichol. Biochemistry 43, 7643-7652.
48. Vishwakarma, R. A. and Menon, A. K. (2005) Flip-flop of glycosylphosphatidylinositols (GPI's) across the ER. Chem. Commun. (Camb): 453-455.
49. Helenius, J., Ng, D. T., Marolda, C. L., Walter, P., Valvano, M. A. and Aebi, M. (2002) Translocation of lipid-linked oligosaccharides across the ER membrane requires Rft1 protein. Nature 415, 447-450.
50. Feldman, M. F., Marolda, C. L., Monteiro, M. A., Perry, M. B., Parodi, A. J. and Valvano, M. A. (1999) The activity of a putative polyisoprenol-linked sugar translocase (Wzx) involved in Escherichia coli O antigen assembly is independent of the chemical structure of the O repeat. J. Biol. Chem. 274, 35129-35138.
51. Samuelson, J., Banerjee, S., Magnelli, P., Cui, J., Kelleher, D. J., Gilmore, R. and Robbins, P. W. (2005) The diversity of dolichol-linked precursors to Asn-linked glycans likely results from secondary loss of sets of glycosyltransferases. Proc. Natl. Acad. Sci. USA 102, 1548-1553.
52. Rick, P. D., Barr, K., Sankaran, K., Kajimura, J., Rush, J. S. and Waechter, C. J. (2003) Evidence that the wzxE gene of Escherichia coli K-12 encodes a protein involved in the transbilayer movement of a trisaccharide-lipid intermediate in the assembly of enterobacterial common antigen. J. Biol. Chem. 278, 16534-16542.
53. Alaimo, C., Catrein, I., Morf, L., Marolda, C. L., Callewaert, N., Valvano, M. A., Feldman, M. F. and Aebi, M. (2006) Two distinct but interchangeable mechanisms for flipping of lipid-linked oligosaccharides. EMBO J. 25, 967-976.
54. Buton, X., Herve, P., Kubelt, J., Tannert, A., Burger, K. N., Fellmann, P., Muller, P., Herrmann, A., Seigneuret, M. and Devaux, P. F. (2002) Transbilayer movement of monohexosylsphingolipids in endoplasmic reticulum and Golgi membranes. Biochemistry 41, 13106-13115.
55. Devaux, P. F. (1993) Phospholipid translocation in the endoplasmic reticulum. Subcell Biochem. 21, 273-285.
56. Devaux, P. F. (1991) Static and dynamic lipid asymmetry in cell membranes. Biochemistry 30, 1163-1173.
57. Cerbon, J. and Calderon, V. (1995) Generation, modulation and maintenance of the plasma membrane asymmetric phospholipid composition in yeast cells during growth: their relation to surface potential and membrane protein activity. Biochim. Biophys. Acta 1235, 100-106.
58. Bucki, R., Janmey, P. A., Vegners, R., Giraud, F. and Sulpice, J. C. (2001) Involvement of phosphatidylinositol 4,5-bisphosphate in phosphatidylserine exposure in platelets: use of a permeant phosphoinositide- binding peptide. Biochemistry 40, 15752-15761.
59. Smeets, E. F., Comfurius, P., Bevers, E. M. and Zwaal, R. F. (1994) Calcium-induced transbilayer scrambling of fluorescent phospholipid analogs in platelets and erythrocytes. Biochim. Biophys. Acta 1195, 281-286.
60. Williamson, P., Bevers, E. M., Smeets, E. F., Comfurius, P., Schlegel, R. A. and Zwaal, R. F. (1995) Continuous analysis of the mechanism of activated transbilayer lipid movement in platelets. Biochemistry 34, 10448-10455.
61. Sims, P. J. and Wiedmer, T. (2001) Unraveling the mysteries of phospholipid scrambling. Thromb. Haemost. 86, 266-275.
62. Gaffet, P., Bettache, N. and Bienvenue, A. (1995) Transverse redistribution of phospholipids during human platelet activation: evidence for a vectorial outflux specific to aminophospholipids. Biochemistry 34, 6762-6769.
63. 2+-induced scrambling of various fluorescently labelled lipid analogues in red blood cells. Biochem. J. 362, 741-747.
64. Fadok, V. A., Bratton, D. L., Rose, D. M., Pearson, A., Ezekewitz, R. A. and Henson, P. M. (2000) A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405, 85-90.
65. Wang, X., Wu, Y. C., Fadok, V. A., Lee, M. C., Gengyo-Ando, K., Cheng, L. C., Ledwich, D., Hsu, P. K., Chen, J. Y., Chou, B. K., Henson, P., Mitani, S. and Xue, D. (2003) Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12. Science 302, 1563-1566.
66. Manodori, A. B., Barabino, G. A., Lubin, B. H. and Kuypers, F. A. (2000) Adherence of phosphatidylserine-exposing erythrocytes to endothelial matrix thrombospondin. Blood 95, 1293-1300.
67. Lentz, B. R. (2003) Exposure of platelet membrane phosphatidylserine regulates blood coagulation. Prog. Lipid Res. 42, 423-438.
68. Gadella, B. M. and Harrison, R. A. (2002) Capacitation induces cyclic adenosine 3′,5′-monophosphate-dependent, but apoptosis-unrelated, exposure of aminophospholipids at the apical head plasma membrane of boar sperm cells. Biol. Reprod. 67, 340-350.
69. van den Eijnde, S. M., van den Hoff, M. J., Reutelingsperger, C. P., van Heerde, W. L., Henfling, M. E., Vermeij-Keers, C., Schutte, B., Borgers, M. and Ramaekers, F. C. (2001) Transient expression of phosphatidylserine at cell-cell contact areas is required for myotube formation. J. Cell Sci. 114, 3631-3642.
70. Tannert, A., Wustner, D., Bechstein, J., Muller, P., Devaux, P. F. and Herrmann, A. (2003) Aminophospholipids have no access to the luminal side of the biliary canaliculus: implications for the specific lipid composition of the bile fluid. J. Biol. Chem. 278, 40631-40639.
71. Emoto, K., Kobayashi, T., Yamaji, A., Aizawa, H., Yahara, I., Inoue, K. and Umeda, M. (1996) Redistribution of phosphatidylethanolamine at the cleavage furrow of dividing cells during cytokinesis. Proc. Natl. Acad. Sci. USA 93, 12867-12872.
72. Emoto, K. and Umeda, M. (2000) An essential role for a membrane lipid in cytokinesis. Regulation of contractile ring disassembly by redistribution of phosphatidylethanolamine. J. Cell Biol. 149, 1215-1224.
73. Elliott, J. I., Surprenant, A., Marelli-Berg, F. M., Cooper, J. C., Cassady-Cain, R. L., Wooding, C., Linton, K., Alexander, D. R. and Higgins, C. F. (2005) Membrane phosphatidylserine distribution as a non-apoptotic signalling mechanism in lymphocytes. Nat. Cell Biol. 7, 808-816.
74. Daleke, D. L. and Huestis, W. H. (1985) Incorporation and translocation of aminophospholipids in human erythrocytes. Biochemistry 24, 5406-5416.
75. Pomorski, T., Holthuis, J. C., Herrmann, A. and van Meer, G. (2004) Tracking down lipid flippases and their biological functions. J. Cell Sci. 117, 805-813.
76. Zachowski, A., Henry, J. P. and Devaux, P. F. (1989) Control of transmembrane lipid asymmetry in chromaffin granules by an ATP-dependent protein. Nature 340, 75-76.
77. Zachowski, A. and Gaudry-Talarmain, Y. M. (1990) Phospholipid transverse diffusion in synaptosomes: evidence for the involvement of the aminophospholipid translocase. J. Neurochem. 55, 1352-1356.
78. Natarajan, P., Wang, J., Hua, Z. and Graham, T. R. (2004) Drs2p-coupled aminophospholipid translocase activity in yeast Golgi membranes and relationship to in vivo function. Proc. Natl. Acad. Sci. USA 101, 10614-10619.
79. Alder-Baerens, N., Lisman, Q., Luong, L., Pomorski, T. and Holthuis, J. C. (2006) Loss of p4 ATPases drs2p and dnf3p disrupts aminophospholipid transport and asymmetry in yeast post-Golgi secretory vesicles. Mol. Biol. Cell 17, 1632-1642.
80. Tang, X., Halleck, M. S., Schlegel, R. A. and Williamson, P. (1996) A subfamily of P-type ATPases with aminophospholipid transporting activity. Science 272, 1495-1497.
81. Paulusma, C. C. and Oude Elferink, R. P. (2005) The type 4 subfamily of P-type ATPases, putative aminophospholipid translocases with a role in human disease. Biochim. Biophys. Acta 1741, 11-24.
82. Gomes, E., Jakobsen, M. K., Axelsen, K. B., Geisler, M. and Palmgren, M. G. (2000) Chilling tolerance in Arabidopsis involves ALA1, a member of a new family of putative aminophospholipid translocases. Plant Cell 12, 2441-2454.
83. Siegmund, A., Grant, A., Angeletti, C., Malone, L., Nichols, J. W. and Rudolph, H. K. (1998) Loss of Drs2p does not abolish transfer of fluorescence-labeled phospholipids across the plasma membrane of Saccharomyces cerevisiae. J. Biol. Chem. 273, 34399-34405.
84. Marx, U., Polakowski, T., Pomorski, T., Lang, C., Nelson, H., Nelson, N. and Herrmann, A. (1999) Rapid transbilayer movement of fluorescent phospholipid analogues in the plasma membrane of endocytosis-deficient yeast cells does not require the Drs2 protein. Eur. J. Biochem. 263, 254-263.
85. Chen, C. Y., Ingram, M. F., Rosal, P. H. and Graham, T. R. (1999) Role for Drs2p, a P-type ATPase and potential aminophospholipid translocase, in yeast late Golgi function. J. Cell Biol. 147, 1223-1236.
86. Gall, W. E., Geething, N. C., Hua, Z., Ingram, M. F., Liu, K., Chen, S. I. and Graham, T. R. (2002) Drs2p-dependent formation of exocytic clathrin-coated vesicles in vivo. Curr. Biol. 12, 1623-1627.
87. Hua, Z., Fatheddin, P. and Graham, T. R. (2002) An essential subfamily of Drs2p-related P-type ATPases is required for protein trafficking between Golgi complex and endosomal/ vacuolar system. Mol. Biol. Cell 13, 3162-3177.
88. Pomorski, T., Lombardi, R., Riezman, H., Devaux, P. F., van Meer, G. and Holthuis, J. C. (2003) Drs2p-related P-type ATPases Dnf1p and Dnf2p are required for phospholipid translocation across the yeast plasma membrane and serve a role in endocytosis. Mol. Biol. Cell 14, 1240-1254.
89. Zoeller, R. A., Layne, M. D. and Modest, E. J. (1995) Animal cell mutants unable to take up biologically active glycerophospholipids. J. Lipid Res. 36, 1866-1875.
90. Muller, P., Pomorski, T., Porwoli, S., Tauber, R. and Herrmann, A. (1996) Transverse movement of spin-labeled phospholipids in the plasma membrane of a hepatocytic cell line (HepG2): implications for biliary lipid secretion. Hepatology 24, 1497-1503.
91. Pomorski, T., Herrmann, A., Muller, P., van Meer, G. and Burger, K. (1999) Protein-mediated inward translocation of phospholipids occurs in both the apical and basolateral plasma membrane domains of epithelial cells. Biochemistry 38, 142-150.
92. Hanson, P. K. and Nichols, J. W. (2001) Energy-dependent flip of fluorescence-labeled phospholipids is regulated by nutrient starvation and transcription factors, PDR1 and PDR3. J. Biol. Chem. 276, 9861-9867.
93. Elvington, S. M., Bu, F. and Nichols, J. W. (2005) Fluorescent, acyl chain-labeled phosphatidylcholine analogs reveal novel transport pathways across the plasma membrane of yeast. J. Biol. Chem. 280, 40957-40964.
94. Perez-Victoria, F. J., Gamarro, F., Ouellette, M. and Castanys, S. (2003) Functional cloning of the miltefosine transporter. A novel P-type phospholipid translocase from Leishmania involved in drug resistance. J. Biol. Chem. 278, 49965-49971.
95. Wang, L., Beserra, C. and Garbers, D. L. (2004) A novel aminophospholipid transporter exclusively expressed in spermatozoa is required for membrane lipid asymmetry and normal fertilization. Dev. Biol. 267, 203-215.
96. Ujhazy, P., Ortiz, D., Misra, S., Li, S., Moseley, J., Jones, H. and Arias, I. M. (2001) Familial intrahepatic cholestasis 1: studies of localization and function. Hepatology 34, 768-775.
97. Moriyama, Y., Nelson, N., Maeda, M. and Futai, M. (1991) Vanadate-sensitive ATPase from chromaffin granule membranes formed a phosphoenzyme intermediate and was activated by phosphatidylserine. Arch. Biochem. Biophys. 286, 252-256.
98. Ding, J., Wu, Z., Crider, B. P., Ma, Y., Li, X., Slaughter, C., Gong, L. and Xie, X. S. (2000) Identification and functional expression of four isoforms of ATPase II, the putative aminophospholipid translocase. Effect of isoform variation on the ATPase activity and phospholipid specificity. J. Biol. Chem. 275, 23378-23386.
99. Paterson, J., Renkema, K., Burden, L., Halleck, M., Schlegel, R. A., Williamson, P. and Daleke, D. L. (2006) Lipid specific activation of the murine P4-ATPase Atp8a1 (ATPase II). Biochemistry 45, 5367-5376.
100. Kato, U., Emoto, K., Fredriksson, C., Nakamura, H., Ohta, A., Kobayashi, T., Murakami-Murofushi, K., Kobayashi, T. and Umeda, M. (2002) A novel membrane protein, Ros3p, is required for phospholipid translocation across the plasma membrane in Saccharomyces cerevisiae. J. Biol. Chem. 277, 37855-37862.
101. Hanson, P. K., Malone, L., Birchmore, J. L. and Nichols, J. W. (2003) Lem3p is essential for the uptake and potency of alkylphosphocholine drugs, edelfosine and miltefosine. J. Biol. Chem. 278, 36041-36050.
102. Geering, K. (2001) The functional role of beta subunits in oligomeric P-type ATPases. J. Bioenerg. Biomembr. 33, 425-438.
103. Saito, K., Fujimura-Kamada, K., Furuta, N., Kato, U., Umeda, M. and Tanaka, K. (2004) Cdc50p, a protein required for polarized growth, associates with the Drs2p P-type ATPase implicated in phospholipid translocation in Saccharomyces cerevisiae. Mol. Biol. Cell 15, 3418-3432.
104. Bitbol, M. and Devaux, P. F. (1988) Measurement of outward translocation of phospholipids across human erythrocyte membrane. Proc. Natl. Acad. Sci. USA 85, 6783-6787.
105. Connor, J., Pak, C. H., Zwaal, R. F. and Schroit, A. J. (1992) Bidirectional transbilayer movement of phospholipid analogs in human red blood cells. Evidence for an ATP-dependent and protein-mediated process. J. Biol. Chem. 267, 19412-19417.
106. Suzuki, H., Kamakura, M., Morii, M. and Takeguchi, N. (1997) The phospholipid flippase activity of gastric vesicles. J. Biol. Chem. 272, 10429-10434.
107. Kalin, N., Fernandes, J., Hrafnsdottir, S. and van Meer, G. (2004) Natural phosphatidylcholine is actively translocated across the plasma membrane to the surface of mammalian cells. J. Biol. Chem. 279, 33228-33236.
108. Smit, J. J., Schinkel, A. H., Oude Elferink, R. P., Groen, A. K., Wagenaar, E., van Deemter, L., Mol, C. A., Ottenhoff, R., van der Lugt, N. M., van Roon, M. A., van der Valk, M. A., Offerhaus, G. J., Berns, A. J. and Borst, P. (1993) Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 75, 451-462.
109. Smith, A. J., Timmermans-Hereijgers, J. L., Roelofsen, B., Wirtz, K. W., van Blitterswijk, W. J., Smit, J. J., Schinkel, A. H. and Borst, P. (1994) The human MDR3 P-glycoprotein promotes translocation of phosphatidylcholine through the plasma membrane of fibroblasts from transgenic mice. FEBS Lett. 354, 263-266.
110. van Helvoort, A., Smith, A. J., Sprong, H., Fritzsche, I., Schinkel, A. H., Borst, P. and van Meer, G. (1996) MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine. Cell 87, 507-517.
111. Bosch, I., Dunussi-Joannopoulos, K., Wu, R. L., Furlong, S. T. and Croop, J. (1997) Phosphatidylcholine and phosphatidylethanolamine behave as substrates of the human MDR1 P-glycoprotein. Biochemistry 36, 5685-5694.
112. Pohl, A., Lage, H., Muller, P., Pomorski, T. and Herrmann, A. (2002) Transport of phosphatidylserine via MDR1 (multidrug resistance 1)P-glycoprotein in a human gastric carcinoma cell line. Biochem. J. 365, 259-268.
113. Eckford, P. D. and Sharom, F. J. (2005) The reconstituted P-glycoprotein multidrug transporter is a flippase for glucosylceramide and other simple glycosphingolipids. Biochem. J. 389, 517-526.
114. Ernest, S. and Bello-Reuss, E. (1999) Secretion of platelet-activating factor is mediated by MDR1 P-glycoprotein in cultured human mesangial cells. J. Am. Soc. Nephrol. 10, 2306-2313.
115. Raggers, R. J., Vogels, I. and van Meer, G. (2001) Multidrug-resistance P-glycoprotein (MDR1) secretes platelet-activating factor. Biochem. J. 357, 859-865.
116. Kamp, D. and Haest, C. W. (1998) Evidence for a role of the multidrug resistance protein (MRP) in the outward translocation of NBD-phospholipids in the erythrocyte membrane. Biochim. Biophys. Acta 1372, 91-101.
117. Raggers, R. J., van Helvoort, A., Evers, R. and van Meer, G. (1999) The human multidrug resistance protein MRP1 translocates sphingolipid analogs across the plasma membrane. J. Cell Sci. 112, 415-422.
118. Dekkers, D. W., Comfurius, P., van Gool, R. G., Bevers, E. M. and Zwaal, R. F. (2000) Multidrug resistance protein 1 regulates lipid asymmetry in erythrocyte membranes. Biochem. J. 350, 531-535.
119. Huang, Z., Chang, X., Riordan, J. R. and Huang, Y. (2004) Fluorescent modified phosphatidylcholine floppase activity of reconstituted multidrug resistance-associated protein MRP1. Biochim. Biophys. Acta 1660, 155-163.
120. Decottignies, A., Grant, A. M., Nichols, J. W., de Wet, H., McIntosh, D. B. and Goffeau, A. (1998) ATPase and multidrug transport activities of the overexpressed yeast ABC protein Yor1p. J. Biol. Chem. 273, 12612-12622.
121. Smriti, Krishnamurthy, S., Dixit, B. L., Gupta, C. M., Milewski, S. and Prasad, R. (2002) ABC transporters Cdr1p, Cdr2p and Cdr3p of a human pathogen Candida albicans are general phospholipid translocators. Yeast 19, 303-318.
122. Dogra, S., Krishnamurthy, S., Gupta, V., Dixit, B. L., Gupta, C. M., Sanglard, D. and Prasad, R. (1999) Asymmetric distribution of phosphatidylethanolamine in C. albicans: possible mediation by CDR1, a multidrug transporter belonging to ATP binding cassette (ABC) superfamily. Yeast 15, 111-121.
123. Hamilton, J. A. (2003) Fast flip-flop of cholesterol and fatty acids in membranes: implications for membrane transport proteins. Curr. Opin. Lipidol. 14, 263-271.
124. Rust, S., Rosier, M., Funke, H., Real, J., Amoura, Z., Piette, J. C., Deleuze, J. F., Brewer, H. B., Duverger, N., Denefle, P. and Assmann, G. (1999) Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1. Nat. Genet. 22, 352-355.
125. Brooks-Wilson, A., Marcil, M., Clee, S. M., Zhang, L. H., Roomp, K., van Dam, M., Yu, L., Brewer, C., Collins, J. A., Molhuizen, H. O., Loubser, O., Ouelette, B. F., Fichter, K., Ashbourne-Excoffon, K. J., Sensen, C. W., Scherer, S., Mott, S., Denis, M., Martindale, D., Frohlich, J., Morgan, K., Koop, B., Pimstone, S., Kastelein, J. J., Genest, J. Jr and Hayden, M. R. (1999) Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat. Genet. 22, 336-345.
126. Bodzioch, M., Orso, E., Klucken, J., Langmann, T., Bottcher, A., Diederich, W., Drobnik, W., Barlage, S., Buchler, C., Porsch-Ozcurumez, M., Kaminski, W. E., Hahmann, H. W., Oette, K., Rothe, G., Aslanidis, C., Lackner, K. J. and Schmitz, G. (1999) The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease. Nat. Genet. 22, 347-351.
127. Hamon, Y., Broccardo, C., Chambenoit, O., Luciani, M. F., Toti, F., Chaslin, S., Freyssinet, J. M., Devaux, P. F., McNeish, J., Marguet, D. and Chimini, G. (2000) ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine. Nat. Cell Biol. 2, 399-406.
128. Chambenoit, O., Hamon, Y., Marguet, D., Rigneault, H., Rosseneu, M. and Chimini, G. (2001) Specific docking of apolipoprotein A-I at the cell surface requires a functional ABCA1 transporter. J. Biol. Chem. 276, 9955-9960.
129. Alder-Baerens, N., Muller, P., Pohl, A., Korte, T., Hamon, Y., Chimini, G., Pomorski, T. and Herrmann, A. (2005) Head-group-specific exposure of phospholipids in ABCA1-expressing cells. J. Biol. Chem. 280, 26321-26329.
130. Small, D. M. (2003) Role of ABC transporters in secretion of cholesterol from liver into bile. Proc. Natl. Acad. Sci. USA 100, 4-6.
131. Takahashi, K., Kimura, Y., Kioka, N., Matsuo, M. and Ueda, K. (2006) Purification and ATPase activity of human ABCA1. J. Biol. Chem. 281, 10760-10768.
132. Yamano, G., Funahashi, H., Kawanami, O., Zhao, L. X., Ban, N., Uchida, Y., Morohoshi, T., Ogawa, J., Shioda, S. and Inagaki, N. (2001) ABCA3 is a lamellar body membrane protein in human lung alveolar type II cells. FEBS Lett. 508, 221-225.
133. Nagata, K., Yamamoto, A., Ban, N., Tanaka, A. R., Matsuo, M., Kioka, N., Inagaki, N. and Ueda, K. (2004) Human ABCA3, a product of a responsible gene for abca3 for fatal surfactant deficiency in newborns, exhibits unique ATP hydrolysis activity and generates intracellular multilamellar vesicles. Biochem. Biophys. Res. Commun. 324, 262-268.
134. Shulenin, S., Nogee, L. M., Annilo, T., Wert, S. E., Whitsett, J. A. and Dean, M. (2004) ABCA3 gene mutations in newborns with fatal surfactant deficiency. N. Engl. J. Med. 350, 1296-1303.
135. Wang, N., Lan, D., Gerbod-Giannone, M., Linsel-Nitschke, P., Jehle, A. W., Chen, W., Martinez, L. O. and Tall, A. R. (2003) ATP-binding cassette transporter A7 (ABCA7) binds apolipoprotein A-I and mediates cellular phospholipid but not cholesterol efflux. J. Biol. Chem. 278, 42906-42912.
136. Abe-Dohmae, S., Ikeda, Y., Matsuo, M., Hayashi, M., Okuhira, K., Ueda, K. and Yokoyama, S. (2004) Human ABCA7 supports apolipoprotein-mediated release of cellular cholesterol and phospholipid to generate high density lipoprotein. J. Biol. Chem. 279, 604-611.
137. Lefevre, C., Audebert, S., Jobard, F., Bouadjar, B., Lakhdar, H., Boughdene-Stambouli, O., Blanchet-Bardon, C., Heilig, R., Foglio, M., Weissenbach, J., Lathrop, M., Prud'homme, J. F. and Fischer, J. (2003) Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2. Hum. Mol. Genet. 12, 2369-2378.
138. Akiyama, M., Sugiyama-Nakagiri, Y., Sakai, K., McMillan, J. R., Goto, M., Arita, K., Tsuji-Abe, Y., Tabata, N., Matsuoka, K., Sasaki, R., Sawamura, D. and Shimizu, H. (2005) Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer. J. Clin. Invest. 115, 1777-1784.
139. Kelsell, D. P., Norgett, E. E., Unsworth, H., Teh, M. T., Cullup, T., Mein, C. A., Dopping-Hepenstal, P. J., Dale, B. A., Tadini, G., Fleckman, P., Stephens, K. G., Sybert, V. P., Mallory, S. B., North, B. V., Witt, D. R., Sprecher, E., Taylor, A. E., Ilchyshyn, A., Kennedy, C. T., Goodyear, H., Moss, C., Paige, D., Harper, J. I., Young, B. D., Leigh, I. M., Eady, R. A. and O'Toole, E. A. (2005) Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis. Am. J. Hum. Genet. 76, 794-803.
140. Lee, M. H., Lu, K., Hazard, S., Yu, H., Shulenin, S., Hidaka, H., Kojima, H., Allikmets, R., Sakuma, N., Pegoraro, R., Srivastava, A. K., Salen, G., Dean, M. and Patel, S. B. (2001) Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nat. Genet. 27, 79-83.
141. Berge, K. E., Tian, H., Graf, G. A., Yu, L., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R. and Hobbs, H. H. (2000) Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 290, 1771-1775.
142. Graf, G. A., Yu, L., Li, W. P., Gerard, R., Tuma, P. L., Cohen, J. C. and Hobbs, H. H. (2003) ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion. J. Biol. Chem. 278, 48275-48282.
143. Langheim, S., Yu, L., von Bergmann, K., Lutjohann, D., Xu, F., Hobbs, H. H. and Cohen, J. C. (2005) ABCG5 and ABCG8 require MDR2 for secretion of cholesterol into bile. J. Lipid Res. 46, 1732-1738.
144. Klucken, J., Buchler, C., Orso, E., Kaminski, W. E., Porsch-Ozcurumez, M., Liebisch, G., Kapinsky, M., Diederich, W., Drobnik, W., Dean, M., Allikmets, R. and Schmitz, G. (2000) ABCG1 (ABC8), the human homolog of the Drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport. Proc. Natl. Acad. Sci. USA 97, 817-822.
145. Wang, N., Lan, D., Chen, W., Matsuura, F. and Tall, A. R. (2004) ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. Proc. Natl. Acad. Sci. USA 101, 9774-9779.
146. Vaughan, A. M. and Oram, J. F. (2005) ABCG1 redistributes cell cholesterol to domains removable by high density lipoprotein but not by lipid-depleted apolipoproteins. J. Biol. Chem. 280, 30150-30157.
147. Karten, B., Campenot, R. B., Vance, D. E. and Vance, J. E. (2006) Expression of ABCG1, but not ABCA1, correlates with cholesterol release by cerebellar astroglia. J. Biol. Chem. 281, 4049-4057.
148. Pighin, J. A., Zheng, H., Balakshin, L. J., Goodman, I. P., Western, T. L., Jetter, R., Kunst, L. and Samuels, A. L. (2004) Plant cuticular lipid export requires an ABC transporter. Science 306, 702-704.
149. Araujo-Santos, J. M., Parodi-Talice, A., Castanys, S. and Gamarro, F.
150. Parodi-Talice, A., Araujo, J. M., Torres, C., Perez-Victoria, J. M., Gamarro, F. and Castanys, S. (2003) The overexpression of a new ABC transporter in Leishmania is related to phospholipid trafficking and reduced infectivity. Biochim. Biophys. Acta 1612, 195-207.
151. Perez-Victoria, J. M., Perez-Victoria, F. J., Parodi-Talice, A., Jimenez, I. A., Ravelo, A. G., Castanys, S. and Gamarro, F. (2001) Alkyl- lysophospholipid resistance in multidrug-resistant Leishmania tropica and chemosensitization by a novel P-glycoprotein-like transporter modulator. Antimicrob. Agents. Chemother. 45, 2468-2474.
152. Wilcox, L. J., Balderes, D. A., Wharton, B., Tinkelenberg, A. H., Rao, G. and Sturley, S. L. (2002) Transcriptional profiling identifies two members of the ATP-binding cassette transporter superfamily required for sterol uptake in yeast. J. Biol. Chem. 277, 32466-32472.
153. Li, Y. and Prinz, W. A. (2004) ATP-binding cassette (ABC) transporters mediate nonvesicular, raft-modulated sterol movement from the plasma membrane to the endoplasmic reticulum. J. Biol. Chem. 279, 45226-45234.
154. Allikmets, R., Shroyer, N. F., Singh, N., Seddon, J. M., Lewis, R. A., Bernstein, P. S., Peiffer, A., Zabriskie, N. A., Li, Y., Hutchinson, A., Dean, M., Lupski, J. R. and Leppert, M. (1997) Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science 277, 1805-1807.
155. Sun, H. and Nathans, J. (1997) Stargardt's ABCR is localized to the disc membrane of retinal rod outer segments. Nat. Genet. 17, 15-16.
156. Weng, J., Mata, N. L., Azarian, S. M., Tzekov, R. T., Birch, D. G. and Travis, G. H. (1999) Insights into the function of Rim protein in photoreceptors and etiology of Stargardt's disease from the phenotype in abcr knockout mice. Cell 98, 13-23.
157. Boujaoude, L. C., Bradshaw-Wilder, C., Mao, C., Cohn, J., Ogretmen, B., Hannun, Y. A. and Obeid, L. M. (2001) Cystic fibrosis transmembrane regulator regulates uptake of sphingoid base phosphates and lysophosphatidic acid: modulation: of cellular activity of sphingosine 1-phosphate. J. Biol. Chem. 276, 35258-35264.
158. Frelet, A. and Klein, M. (2006) Insight in eukaryotic ABC transporter function by mutation analysis. FEBS Lett. 580, 1064-1084.
159. Karow, M. and Georgopoulos, C. (1993) The essential Escherichia coli msbA gene, a multicopy suppressor of null mutations in the htrB gene, is related to the universally conserved family of ATP-dependent translocators. Mol. Microbiol. 7, 69-79.
160. Zhou, Z., White, K. A., Polissi, A., Georgopoulos, C. and Raetz, C. R. (1998) Function of Escherichia coli MsbA, an essential ABC family transporter, in lipid A and phospholipid biosynthesis. J. Biol. Chem. 273, 12466-12475.
161. Doerrler, W. T., Reedy, M. C. and Raetz, C. R. (2001) An Escherichia coli mutant defective in lipid export. J. Biol. Chem. 276, 11461-11464.
162. Reyes, C. L., Ward, A., Yu, J. and Chang, G. (2006) The structures of MsbA: Insight into ABC transporter-mediated multidrug efflux. FEBS Lett. 580, 1042-1048.
163. Tefsen, B., Bos, M. P., Beckers, F., Tommassen, J. and de Cock, H. (2005) MsbA is not required for phospholipid transport in Neisseria meningitidis. J. Biol. Chem. 280, 35961-35966.
164. Pohl, A., Devaux, P. F. and Herrmann, A. (2005) Function of prokaryotic and eukaryotic ABC proteins in lipid transport. Biochim. Biophys. Acta 1733, 29-52.
165. van Meer, G., Halter, D., Sprong, H., Somerharju, P. and Egmond, M. R. (2006) ABC lipid transporters: extruders, flippases, or flopless activators? FEBS Lett. 580, 1171-1177.
166. Fitzgerald, M. L., Morris, A. L., Rhee, J. S., Andersson, L. P., Mendez, A. J. and Freeman, M. W. (2002) Naturally occurring mutations in the largest extracellular loops of ABCA1 can disrupt its direct interaction with apolipoprotein A-I. J. Biol. Chem. 277, 33178-33187.
167. Kean, L. S., Grant, A. M., Angeletti, C., Mahe, Y., Kuchler, K., Fuller, R. S. and Nichols, J. W. (1997) Plasma membrane translocation of fluorescent-labeled phosphatidylethanolamine is controlled by transcription regulators, PDR1 and PDR3. J. Cell Biol. 138, 255-270.
168. Zha, X., Genest, J. Jr. and McPherson, R. (2001) Endocytosis is enhanced in Tangier fibroblasts: possible role of ATP-binding cassette protein A1 in endosomal vesicular transport. J. Biol. Chem. 276, 39476-39483.
169. Sheetz, M. P. and Singer, S. J. (1974) Biological membranes as bilayer couples. A molecular mechanism of drug-erythrocyte interactions. Proc. Natl. Acad. Sci. USA 71, 4457-4461.
170. Voeltz, G. K., Prinz, W. A., Shibata, Y., Rist, J. M. and Rapoport, T. A. (2006) A class of membrane proteins shaping the tubular endoplasmic reticulum. Cell 124, 573-586.
171. Birchmeier, W., Lanz, J. H., Winterhalter, K. H. and Conrad, M. J. (1979) ATP-induced endocytosis in human erythrocyte ghosts. Characterization of the process and isolation of the endocytosed vesicles. J. Biol. Chem. 254, 9298-9304.
172. Muller, P., Pomorski, T. and Herrmann, A. (1994) Incorporation of phospholipid analogues into the plasma membrane affects ATP-induced vesiculation of human erythrocyte ghosts. Biochem. Biophys. Res. Commun. 199, 881-887.
173. Farge, E., Ojcius, D. M., Subtil, A. and Dautry-Varsat, A. (1999) Enhancement of endocytosis due to aminophospholipid transport across the plasma membrane of living cells. Am. J. Physiol. 276, C725-733.
174. Rauch, C. and Farge, E. (2000) Endocytosis switch controlled by transmembrane osmotic pressure and phospholipid number asymmetry. Biophys. J. 78, 3036-3047.
175. Chantalat, S., Park, S. K., Hua, Z., Liu, K., Gobin, R., Peyroche, A., Rambourg, A., Graham, T. R. and Jackson, C. L. (2004) The Arf activator Gea2p and the P-type ATPase Drs2p interact at the Golgi in Saccharomyces cerevisiae. J. Cell Sci. 117, 711-722.
176. Wicky, S., Schwarz, H. and Singer-Kruger, B. (2004) Molecular interactions of yeast Neo1p, an essential member of the Drs2 family of aminophospholipid translocases, and its role in membrane trafficking within the endomembrane system. Mol. Cell Biol. 24, 7402-7418.
177. Zhou, Q., Zhao, J., Stout, J. G., Luhm, R. A., Wiedmer, T. and Sims, P. J. (1997) Molecular cloning of human plasma membrane phospholipid scramblase. A protein mediating transbilayer movement of plasma membrane phospholipids. J. Biol. Chem. 272, 18240-18244.
178. Lopez-Montero, I., Rodriguez, N., Cribier, S., Pohl, A., Velez, M. and Devaux, P. F. (2005) Rapid transbilayer movement of ceramides in phospholipid vesicles and in human erythrocytes. J. Biol. Chem. 280, 25811-25819.