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Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

  • Joost C. M. Holthuis
  • Chiara Luberto
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 688)

Abstract

In the last five years tremendous progress has been made toward the understanding of the mechanisms that govern sphingomyelin (SM) synthesis in animal cells. In line with the complexity of most biological processes, also in the case of SM biosynthesis, the more we learn the more enigmatic and finely tuned the system appears. Therefore with this review we aim first, at highlighting the most significant discoveries that advanced our knowledge and understanding of SM biosynthesis, starting from the discovery of SM to the identification of the enzymes responsible for its production; and second, at discussing old and new riddles that such discoveries pose to current investigators.

Keywords

Ulatory Molecule Putative Active Site Residue FFAT Motif Liver Nuclear Membrane Synaptic Plasma Membrane Vesicle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Thudichum JLW. A treatise on the chemical constitution of the brain. 1884 Baillière, Tindall and Cox, London. Republished in 1962 by Archon Books, Hamden, Connecticut.Google Scholar
  2. 2.
    Sribney M, Kennedy EP. The enzymatic synthesis of sphingomyelin. J Biol Chem 1958; 233(6):1315–1322.PubMedGoogle Scholar
  3. 3.
    Weiss SB, Smith SW, Kennedy EP. The enzymatic formation of lecithin from cytidine diphosphate choline and D-1,2-diglyceride. J Biol Chem 1958; 231(1):53–64.PubMedGoogle Scholar
  4. 4.
    Brady RO, Bradley RM, Young OM et al. An alternative pathway for the enzymatic synthesis of sphingomyelin. J Biol Chem 1965; 240(9):3693–3694.PubMedGoogle Scholar
  5. 5.
    Fujino Y, Negishi T. Investigation of the enzymatic synthesis of sphingomyelin. Biochim Biophys Acta 1968; 152(2):428–430.PubMedGoogle Scholar
  6. 6.
    Fujino Y, Nakano M, Negishi T et al. Substrate specificity for ceramide in the enzymatic formation of sphingomyelin. J Biol Chem 1968; 243(17):4650–4651.PubMedGoogle Scholar
  7. 7.
    Sribney M. Stimulation of sphingomyelin synthetase by sulfhydryl reagents. Can J Biochem 1971; 49(3):306–310.CrossRefPubMedGoogle Scholar
  8. 8.
    Diringer H, Marggraf WD, Koch MA et al. Evidence for a new biosynthetic pathway of sphingomyelin in SV 40 transformed mouse cells. Biochem Biophys Res Commun 1972; 47(6):1345–1352.CrossRefPubMedGoogle Scholar
  9. 9.
    Ullman MD, Radin NS. The enzymatic formation of sphingomyelin from ceramide and lecithin in mouse liver. J Biol Chem 1974; 249(5):1506–1512.PubMedGoogle Scholar
  10. 10.
    Stoffel W, Melzner I. Studies in vitro on the biosynthesis of ceramide and sphingomyelin. A reevaluation of proposed pathways. Hoppe Seylers Z Physiol Chem 1980; 361(5):755–771.PubMedGoogle Scholar
  11. 11.
    Marggraf WD, Anderer FA, Kanfer JN. The formation of sphingomyelin from phosphatidylcholine in plasma membrane preparations from mouse fibroblasts. Biochim Biophys Acta 1981; 664(1):61–73.PubMedGoogle Scholar
  12. 12.
    Voelker DR, Kennedy EP. Cellular and enzymic synthesis of sphingomyelin. Biochemistry 1982; 21(11):2753–2759.CrossRefPubMedGoogle Scholar
  13. 13.
    Nelson DH, Murray DK. Dexamethasone increases the synthesis of sphingomyelin in 3T3-L1 cell membranes. Proc Natl Acad Sci USA 1982; 79(21):6690–6692.CrossRefPubMedGoogle Scholar
  14. 14.
    Marggraf WD, Zertani R, Anderer FA et al. The role of endogenous phosphatidylcholine and ceramide in the biosynthesis of sphingomyelin in mouse fibroblasts. Biochim Biophys Acta 1982; 710(3):314–323.PubMedGoogle Scholar
  15. 15.
    Lipsky NG, Pagano RE. Sphingolipid metabolism in cultured fibroblasts: microscopic and biochemical studies employing a fluorescent ceramide analogue. Proc Natl Acad Sci USA 1983; 80(9):2608–2612.CrossRefPubMedGoogle Scholar
  16. 16.
    Lipsky NG, Pagano RE. Intracellular translocation of fluorescent sphingolipids in cultured fibroblasts: endogenously synthesized sphingomyelin and glucocerebroside analogues pass through the Golgi apparatus en route to the plasma membrane. J Cell Biol 1985; 100(1):27–34.CrossRefPubMedGoogle Scholar
  17. 17.
    van Meer G, Stelzer EH, Wijnaendts-van-Resandt RW et al. Sorting of sphingolipids in epithelial (Madin-Darby canine kidney) cells. J Cell Biol 1987; 105(4):1623–1635.CrossRefPubMedGoogle Scholar
  18. 18.
    Futerman AH, Stieger B, Hubbard AL et al. Sphingomyelin synthesis in rat liver occurs predominantly at the cis and medial cisternae of the Golgi apparatus. J Biol Chem 1990; 265(15):8650–8657.PubMedGoogle Scholar
  19. 19.
    Jeckel D, Karrenbauer A, Birk R et al. Sphingomyelin is synthesized in the cis Golgi. FEBS Lett 1990; 261(1):155–157.CrossRefPubMedGoogle Scholar
  20. 20.
    Jeckel D, Karrenbauer A, Burger KN et al. Glucosylceramide is synthesized at the cytosolic surface of various Golgi subfractions. J Cell Biol 1992; 117(2):259–267.CrossRefPubMedGoogle Scholar
  21. 21.
    Kallen KJ, Quinn P, Allan D. Effects of brefeldin A on sphingomyelin transport and lipid synthesis in BHK21 cells. Biochem J 1993; 289(Pt 1):307–312.PubMedGoogle Scholar
  22. 22.
    Allan D, Kallen KJ, Quinn P. Biosynthesis of sphingomyelin and its delivery to the surface of baby hamster kidney (BHK) cells. Biochem Soc Trans 1993; 21(2):240–244.PubMedGoogle Scholar
  23. 23.
    Kallen KJ, Allan D, Whatmore J et al. Synthesis of surface sphingomyelin in the plasma membrane recycling pathway of BHK cells. Biochim Biophys Acta 1994; 1191(1):52–58.CrossRefPubMedGoogle Scholar
  24. 24.
    van Helvoort A, Stoorvogel W, van Meer G et al. Sphingomyelin synthase is absent from endosomes. J Cell Sci 1997; 110(Pt 6):781–788.PubMedGoogle Scholar
  25. 25.
    Schweizer A, Clausen H, van Meer G et al. Localization of O-glycan initiation, sphingomyelin synthesis and glucosylceramide synthesis in Vero cells with respect to the endoplasmic reticulum-Golgi intermediate compartment. J Biol Chem 1994; 269(6):4035–4041.PubMedGoogle Scholar
  26. 26.
    Hofmeister R, Bottcher A, Schmitz G. Preparation of Golgi subfractions with free-solution isotachophoresis: analysis of sphingomyelin synthesis in Golgi subfractions from rat liver. Electrophoresis 1998; 19(7):1185–1194.CrossRefPubMedGoogle Scholar
  27. 27.
    Allan D, Obradors MJ. Enzyme distributions in subcellular fractions of BHK cells infected with Semliki forest virus: evidence for a major fraction of sphingomyelin synthase in the trans-golgi network. Biochim Biophys Acta 1999; 1450(3):277–287.PubMedGoogle Scholar
  28. 28.
    Sadeghlar F, Sandhoff K, van Echten-Deckert G. Cell type specific localization of sphingomyelin biosynthesis. FEBS Lett 2000; 478(1–2):9–12.CrossRefGoogle Scholar
  29. 29.
    Hanada K, Hara T, Fukasawa M et al. Mammalian cell mutants resistant to a sphingomyelin-directed cytolysin. Genetic and biochemical evidence for complex formation of the LCB1 protein with the LCB2 protein for serine palmitoyltransferase. J Biol Chem 1998; 273(50):33787–33794.CrossRefPubMedGoogle Scholar
  30. 30.
    Hanada K, Kumagai K, Yasuda S et al. Molecular machinery for nonvesicular trafficking of ceramide. Nature 2003; 426(6968):803–809.CrossRefPubMedGoogle Scholar
  31. 31.
    Raya A, Revert-Ros F, Martinez-Martinez P et al. Goodpasture antigen-binding protein, the kinase that phosphorylates the goodpasture antigen, is an alternatively spliced variant implicated in autoimmune pathogenesis. J Biol Chem 2000; 275(51):40392–40399.CrossRefPubMedGoogle Scholar
  32. 32.
    Kawano M, Kumagai K, Nishijima M et al. Efficient trafficking of ceramide from the endoplasmic reticulum to the Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif of CERT. J Biol Chem 2006; 281(40):30279–30288.CrossRefPubMedGoogle Scholar
  33. 33.
    Kumagai K, Yasuda S, Okemoto K et al. CERT mediates intermembrane transfer of various molecular species of ceramides. J Biol Chem 2005; 280(8):6488–6495.CrossRefPubMedGoogle Scholar
  34. 34.
    Fukasawa M, Nishijima M, Hanada K. Genetic evidence for ATP-dependent endoplasmic reticulum-to-Golgi apparatus trafficking of ceramide for sphingomyelin synthesis in Chinese hamster ovary cells. J Cell Biol 1999; 144(4):673–685.CrossRefPubMedGoogle Scholar
  35. 35.
    Funakoshi T, Yasuda S, Fukasawa M et al. Reconstitution of ATP-and cytosol-dependent transport of de novo synthesized ceramide to the site of sphingomyelin synthesis in semi-intact cells. J Biol Chem 2000; 275(39):29938–29945.CrossRefPubMedGoogle Scholar
  36. 36.
    Hanada K, Kumagai K, Tomishige N et al. CERT and intracellular trafficking of ceramide. Biochim Biophys Acta 2007; 1771(6):644–653.PubMedGoogle Scholar
  37. 37.
    Ladinsky MS, Mastronarde DN, McIntosh JR et al. Golgi structure in three dimensions: functional insights from the normal rat kidney cell. J Cell Biol 1999; 144(6):1135–1149.CrossRefPubMedGoogle Scholar
  38. 38.
    Mogelsvang S, Marsh BJ, Ladinsky MS et al. Predicting function from structure: 3D structure studies of the mammalian Golgi complex. Traffic 2004; 5(5):338–345.CrossRefPubMedGoogle Scholar
  39. 39.
    Giussani P, Colleoni T, Brioschi L et al. Ceramide traffic in C6 glioma cells: evidence for CERT-dependent and independent transport from ER to the Golgi apparatus. Biochim Biophys Acta 2008; 1781(1–2):40–51.Google Scholar
  40. 40.
    Broad TE, Dawson RM. Formation of ceramide phosphorylethanolamine from phosphatidylethanolamine in the rumen protozoon Entodinium caudatum (Short Communication). Biochem J 1973; 134(2):659–662.PubMedGoogle Scholar
  41. 41.
    Malgat M, Maurice A, Baraud J. Sphingomyelin and ceramide-phosphoethanolamine synthesis by microsomes and plasma membranes from rat liver and brain. J Lipid Res 1986; 27(3):251–260.PubMedGoogle Scholar
  42. 42.
    Malgat M, Maurice A, Baraud J. Sidedness of ceramide-phosphoethanolamine synthesis on rat liver and brain microsomal membranes. J Lipid Res 1987; 28(2):138–143.PubMedGoogle Scholar
  43. 43.
    Hinkovska-Galcheva V, Petkova DH, Nikolova MN. Sphingomyelin and ceramide: phosphoethanolamine synthesis in ram spermatozoa plasma membrane. Int J Biochem. 1989; 21(10):1153–1156.CrossRefPubMedGoogle Scholar
  44. 44.
    Maurice A, Malgat M. Evidence for the biosynthesis of ceramide-phosphoethanolamine in brain synaptic plasma membrane vesicles and in sciatic nerve microsomes from normal and Trembler mice. Neurosci Lett 1990; 118(2):177–180.CrossRefPubMedGoogle Scholar
  45. 45.
    Nagiec MM, Nagiec EE, Baltisberger JA et al. Sphingolipid synthesis as a target for antifungal drugs. Complementation of the inositol phosphorylceramide synthase defect in a mutant strain of Saccharomyces cerevisiae by the AUR1 gene. J Biol Chem 1997; 272(15):9809–9817.CrossRefPubMedGoogle Scholar
  46. 46.
    Dickson RC, Sumanasekera C, Lester RL. Functions and metabolism of sphingolipids in Saccharomyces cerevisiae. Prog Lipid Res 2006; 45(6):447–465.CrossRefPubMedGoogle Scholar
  47. 47.
    Sutterwala SS, Hsu FF, Sevova ES et al. Developmentally regulated sphingolipid synthesis in African trypanosomes. Mol Microbiol 2008; 70(2):281–296.CrossRefPubMedGoogle Scholar
  48. 48.
    Barenholz Y, Thompson TE. Sphingomyelins in bilayers and biological membranes. Biochim Biophys Acta 1980; 604(2):129–158.CrossRefPubMedGoogle Scholar
  49. 49.
    Merrill AH, Jr., Sullards MC, Allegood JC et al. Sphingolipidomics: high-throughput, structure-specific and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry. Methods 2005; 36(2):207–224.CrossRefPubMedGoogle Scholar
  50. 50.
    Yang K, Zhao Z, Gross RW et al. Systematic analysis of choline-containing phospholipids using multi-dimensional mass spectrometry-based shotgun lipidomics. J Chromatogr B Analyt Technol Biomed Life Sci 2009.Google Scholar
  51. 51.
    Guo W, Kurze V, Huber T et al. A solid-state NMR study of phospholipid-cholesterol interactions: sphingomyelin-cholesterol binary systems. Biophys J 2002; 83(3):1465–1478.CrossRefPubMedGoogle Scholar
  52. 52.
    Chiu SW, Vasudevan S, Jakobsson E et al. Structure of sphingomyelin bilayers: a simulation study. Biophys J 2003; 85(6):3624–3635.CrossRefPubMedGoogle Scholar
  53. 53.
    Aittoniemi J, Niemela PS, Hyvonen MT et al. Insight into the putative specific interactions between cholesterol, sphingomyelin and palmitoyl-oleoyl phosphatidylcholine. Biophys J 2007; 92(4):1125–1137.CrossRefPubMedGoogle Scholar
  54. 54.
    Ikonen E. Cellular cholesterol trafficking and compartmentalization. Nat Rev Mol Cell Biol 2008; 9(2):125–138.CrossRefPubMedGoogle Scholar
  55. 55.
    van Meer G, Voelker DR, Feigenson GW. Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 2008; 9(2):112–124.CrossRefPubMedGoogle Scholar
  56. 56.
    Luberto C, Stonehouse MJ, Collins EA et al. Purification, characterization and identification of a sphingomyelin synthase from Pseudomonas aeruginosa. PlcH is a multifunctional enzyme. J Biol Chem 2003; 278(35):32733–32743.CrossRefPubMedGoogle Scholar
  57. 57.
    Heidler SA, Radding JA. Inositol phosphoryl transferases from human pathogenic fungi. Biochim Biophys Acta 2000; 1500(1):147–152.PubMedGoogle Scholar
  58. 58.
    Huitema K, van den Dikkenberg J, Brouwers JF et al. Identification of a family of animal sphingomyelin synthases. Embo J 2004; 23(1):33–44.CrossRefPubMedGoogle Scholar
  59. 59.
    Yamaoka S, Miyaji M, Kitano T et al. Expression cloning of a human cDNA restoring sphingomyelin synthesis and cell growth in sphingomyelin synthase-defective lymphoid cells. J Biol Chem 2004; 279(18):18688–18693.CrossRefPubMedGoogle Scholar
  60. 60.
    Vladychenskaya IP, Dergunova LV, Limborska SA. In vitro and in silico analysis of the predicted human MOB gene encoding a phylogenetically conserved transmembrane protein. Biomol Eng 2002; 18(6):263–268.CrossRefPubMedGoogle Scholar
  61. 61.
    Vladychenskaya IP, Dergunova LV, Dmitrieva VG et al. Human gene MOB: structure specification and aspects of transcriptional activity. Gene 2004; 338(2):257–265.CrossRefPubMedGoogle Scholar
  62. 62.
    Yang Z, Jean-Baptiste G, Khoury C et al. The mouse sphingomyelin synthase 1 (SMS1) gene is alternatively spliced to yield multiple transcripts and proteins. Gene 2005; 363:123–132.CrossRefPubMedGoogle Scholar
  63. 63.
    Neuwald AF. An unexpected structural relationship between integral membrane phosphatases and soluble haloperoxidases. Protein Sci 1997; 6(8):1764–1767.CrossRefPubMedGoogle Scholar
  64. 64.
    Yeang C, Varshney S, Wang R et al. The domain responsible for sphingomyelin synthase (SMS) activity. Biochim Biophys Acta 2008; 1781(10):610–617.PubMedGoogle Scholar
  65. 65.
    Kim CA, Bowie JU. SAM domains: uniform structure, diversity of function. Trends Biochem Sci 2003; 28(12):625–628.CrossRefPubMedGoogle Scholar
  66. 66.
    Tafesse FG, Huitema K, Hermansson M et al. Both sphingomyelin synthases SMS1 and SMS2 are required for sphingomyelin homeostasis and growth in human HeLa cells. J Biol Chem 2007; 282(24):17537–17547.CrossRefPubMedGoogle Scholar
  67. 67.
    Rietveld A, Neutz S, Simons K et al. Association of sterol-and glycosylphosphatidylinositol-linked proteins with Drosophila raft lipid microdomains. J Biol Chem 1999; 274(17):12049–12054.CrossRefPubMedGoogle Scholar
  68. 68.
    Rao RP, Yuan C, Allegood JC et al. Ceramide transfer protein function is essential for normal oxidative stress response and lifespan. Proc Natl Acad Sci USA 2007; 104(27):11364–11369.CrossRefPubMedGoogle Scholar
  69. 69.
    Vacaru AM, Tafesse FG, Ternes P et al. Sphingomyelin synthase-related protein SMSr controls ceramide homeostasis in the ER. J Cell Biol 2009; 185(6):1013–1027.CrossRefPubMedGoogle Scholar
  70. 70.
    Vance JE. Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids. J Lipid Res 2008; 49(7):1377–1387.CrossRefPubMedGoogle Scholar
  71. 71.
    Ternes P, Brouwers JF, van den Dikkenberg J et al. Sphingomyelin synthase SMS2 displays dual activity as ceramide phosphoethanolamine synthase. J Lipid Res 2009.Google Scholar
  72. 72.
    Li Z, Hailemariam TK, Zhou H et al. Inhibition of sphingomyelin synthase (SMS) affects intracellular sphingomyelin accumulation and plasma membrane lipid organization. Biochim Biophys Acta 2007; 1771(9):1186–1194.PubMedGoogle Scholar
  73. 73.
    Van der Luit AH, Budde M, Zerp S et al. Resistance to alkyl-lysophospholipid-induced apoptosis due to downregulated sphingomyelin synthase 1 expression with consequent sphingomyelin-and cholesterol-deficiency in lipid rafts. Biochem J 2007; 401(2):541–549.CrossRefPubMedGoogle Scholar
  74. 74.
    Villani M, Subathra M, Im YB et al. Sphingomyelin synthases regulate production of diacylglycerol at the Golgi. Biochem J 2008; 414(1):31–41.CrossRefPubMedGoogle Scholar
  75. 75.
    Miyaji M, Jin ZX, Yamaoka S et al. Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis. J Exp Med 2005; 202(2):249–259.CrossRefPubMedGoogle Scholar
  76. 76.
    Hailemariam TK, Huan C, Liu J et al. Sphingomyelin synthase 2 deficiency attenuates NFkappaB activation. Arterioscler Thromb Vasc Biol 2008; 28(8):1519–1526.CrossRefPubMedGoogle Scholar
  77. 77.
    Ding T, Li Z, Hailemariam T et al. SMS over expression and knockdown: impact on cellular sphingomyelin and diacylglycerol metabolism and cell apoptosis. J Lipid Res 2008; 49(2):376–385.CrossRefPubMedGoogle Scholar
  78. 78.
    Luberto C, Hannun YA. Sphingomyelin synthase, a potential regulator of intracellular levels of ceramide and diacylglycerol during SV40 transformation. Does sphingomyelin synthase account for the putative phosphatidylcholine-specific phospholipase C? J Biol Chem 1998; 273(23):14550–14559.CrossRefPubMedGoogle Scholar
  79. 79.
    Jin ZX, Huang CR, Dong L et al. Impaired TCR signaling through dysfunction of lipid rafts in sphingomyelin synthase 1 (SMS1)-knockdown T-cells. Int Immunol 2008; 20(11):1427–1437.CrossRefPubMedGoogle Scholar
  80. 80.
    Tafesse FG, Ternes P, Holthuis JC. The multigenic sphingomyelin synthase family. J Biol Chem 2006; 281(40):29421–29425.CrossRefPubMedGoogle Scholar
  81. 81.
    Separovic D, Hanada K, Maitah MY et al. Sphingomyelin synthase 1 suppresses ceramide production and apoptosis postphotodamage. Biochem Biophys Res Commun 2007; 358(1):196–202.CrossRefPubMedGoogle Scholar
  82. 82.
    Separovic D, Semaan L, Tarca AL et al. Suppression of sphingomyelin synthase 1 by small interference RNA is associated with enhanced ceramide production and apoptosis after photodamage. Exp Cell Res 2008; 314(8):1860–1868.CrossRefPubMedGoogle Scholar
  83. 83.
    Yang Z, Khoury C, Jean-Baptiste G et al. Identification of mouse sphingomyelin synthase 1 as a suppressor of Bax-mediated cell death in yeast. FEMS Yeast Res 2006; 6(5):751–762.CrossRefPubMedGoogle Scholar
  84. 84.
    Pagano RE. What is the fate of diacylglycerol produced at the Golgi apparatus? Trends Biochem Sci 1988; 13(6):202–205.CrossRefPubMedGoogle Scholar
  85. 85.
    Baron CL, Malhotra V. Role of diacylglycerol in PKD recruitment to the TGN and protein transport to the plasma membrane. Science 2002; 295(5553):325–328.CrossRefPubMedGoogle Scholar
  86. 86.
    Keenan TW, Berezney R, Crane FL. Lipid composition of further purified bovine liver nuclear membranes. Lipids 1972; 7(3):212–215.CrossRefPubMedGoogle Scholar
  87. 87.
    James JL, Clawson GA, Chan CH et al. Analysis of the phospholipid of the nuclear envelope and endoplasmic reticulum of liver cells by high pressure liquid chromatography. Lipids 1981; 16(7):541–545.CrossRefPubMedGoogle Scholar
  88. 88.
    Albi E, Mersel M, Leray C et al. Rat liver chromatin phospholipids. Lipids 1994; 29(10):715–719.CrossRefPubMedGoogle Scholar
  89. 89.
    Albi E, Magni MV. Sphingomyelin synthase in rat liver nuclear membrane and chromatin. FEBS Lett 1999; 460(2):369–372.CrossRefPubMedGoogle Scholar
  90. 90.
    Albi E, Pieroni S, Viola Magni MP et al. Chromatin sphingomyelin changes in cell proliferation and/or apoptosis induced by ciprofibrate. J Cell Physiol 2003; 196(2):354–361.CrossRefPubMedGoogle Scholar
  91. 91.
    Albi E, Cataldi S, Bartoccini E et al. Nuclear sphingomyelin pathway in serum deprivation-induced apoptosis of embryonic hippocampal cells. J Cell Physiol 2006; 206(1):189–195.CrossRefPubMedGoogle Scholar
  92. 92.
    Micheli M, Albi E, Leray C et al. Nuclear sphingomyelin protects RNA from RNase action. FEBS Lett 1998; 431(3):443–447CrossRefPubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  1. 1.Membrane Enzymology Bijvoet Center and Institute of BiomembranesUtrecht UniversityUtrechtThe Netherlands
  2. 2.Departments of Biochemistry and Molecular BiologyMedical University of South CarolinaCharlestonUSA

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