Neurochemical Research

, Volume 41, Issue 1–2, pp 130–143 | Cite as

The Role of 3-O-Sulfogalactosylceramide, Sulfatide, in the Lateral Organization of Myelin Membrane

  • Sara Grassi
  • Simona Prioni
  • Livia Cabitta
  • Massimo Aureli
  • Sandro Sonnino
  • Alessandro Prinetti
Original Paper


Sulfatide (3-O-sulfogalactosylceramide, SM4s) was isolated by Thudichum from the human brain in 1884. Together with galactosylceramide, its direct metabolic precursor in the biosynthetic pathway, sulfatide is highly enriched in myelin in the central and peripheral nervous system, and it has been implicated in several aspects of the biology of myelin-forming cells. Studies obtained using galactolipid-deficient mice strongly support the notion that sulfatide plays critical roles in the correct structure and function of myelin membrane. A number of papers are suggesting that these roles are mediated by a specific function of sulfatide in the lateral organization of myelin membrane, thus affecting the sorting, lateral assembly, membrane dynamics and also the function of specific myelin proteins in different substructures of the myelin sheath. The consequences of altered sulfatide metabolism and sulfatide-mediated myelin organization with respect to myelin diseases are still poorly understood, but it’s very likely that sulfatide might represent not only a critical player in the pathogenesis of several diseases, including multiple sclerosis and Alzheimer’s disease, but also a potentially promising therapeutic target.


Sulfatide Lipid rafts Lipid membrane domains Sphingolipids Multiple sclerosis 



Alzheimer’s disease


UDP-galactose ceramide galactosyltransferase


Central nervous system


Cerebroside sulfotransferase


Detergent-resistant membrane


Extracellular matrix






Myelin-associated glycoprotein


Myelin basic protein


Myelin/oligodendrocyte glycoprotein


Multiple sclerosis


Neural cell adhesion molecule


Neurofascin 155






Proteolipid protein


Peripheral nervous system






3-O-sulfogalactosylceramide (SM4s)




  1. 1.
    IUPAC-IUB Joint Commission on Biochemical Nomenclature (1998) Nomenclature of glycolipids. Carbohydr Res 312:167–175CrossRefGoogle Scholar
  2. 2.
    Snaidero N, Mobius W, Czopka T, Hekking LH, Mathisen C, Verkleij D, Goebbels S, Edgar J, Merkler D, Lyons DA, Nave KA, Simons M (2014) Myelin membrane wrapping of CNS axons by PI(3,4,5)P3-dependent polarized growth at the inner tongue. Cell 156:277–290PubMedCrossRefGoogle Scholar
  3. 3.
    Chrast R, Saher G, Nave KA, Verheijen MH (2011) Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models. J Lipid Res 52:419–434PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    O’Brien JS, Sampson EL (1965) Lipid composition of the normal human brain: gray matter, white matter, and myelin. J Lipid Res 6:537–544PubMedGoogle Scholar
  5. 5.
    Jackman N, Ishii A, Bansal R (2009) Oligodendrocyte development and myelin biogenesis: parsing out the roles of glycosphingolipids. Physiology (Bethesda) 24:290–297CrossRefGoogle Scholar
  6. 6.
    Taylor CM, Marta CB, Bansal R, Pfeiffer SE (2004) The transport, assembly and function of myelin lipids. Myelin Biol Disord 1:57–88Google Scholar
  7. 7.
    Saher G, Quintes S, Nave KA (2011) Cholesterol: a novel regulatory role in myelin formation. Neuroscientist 17:79–93PubMedCrossRefGoogle Scholar
  8. 8.
    Stoffel W, Bosio A (1997) Myelin glycolipids and their functions. Curr Opin Neurobiol 7:654–661PubMedCrossRefGoogle Scholar
  9. 9.
    Eckhardt M (2008) The role and metabolism of sulfatide in the nervous system. Mol Neurobiol 37:93–103PubMedCrossRefGoogle Scholar
  10. 10.
    Honke K (2013) Biosynthesis and biological function of sulfoglycolipids. Proc Jpn Acad Ser B Phys Biol Sci 89:129–138PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Sonnino S, Prinetti A (2013) Membrane domains and the “lipid raft” concept. Curr Med Chem 20:4–21PubMedGoogle Scholar
  12. 12.
    Sonnino S, Prinetti A (2010) Lipids and membrane lateral organization. Front Physiol 1:153PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Maggio B (1997) Molecular interactions of the major myelin glycosphingolipids and myelin basic protein in model membranes. Neurochem Res 22:475–481PubMedCrossRefGoogle Scholar
  14. 14.
    Viani P, Marchesini S, Cervato G, Cestaro B (1986) Calorimetric properties of mixtures of distearoylphosphatidylcholine and sulfatides with definite fatty acid composition. Biochem Int 12:125–135PubMedGoogle Scholar
  15. 15.
    Boggs JM, Mulholland D, Koshy KM (1990) Mixtures of semisynthetic species of cerebroside sulfate with dipalmitoyl phosphatidylcholine. Thermotropic phase behavior and permeability. Biochem Cell Biol 68:70–82PubMedCrossRefGoogle Scholar
  16. 16.
    Boggs JM, Koshy KM, Rangaraj G (1993) Thermotropic phase behavior of mixtures of long chain fatty acid species of cerebroside sulfate with different fatty acid chain length species of phospholipid. Biochemistry 32:8908–8922PubMedCrossRefGoogle Scholar
  17. 17.
    Ruettinger A, Kiselev MA, Hauss T, Dante S, Balagurov AM, Neubert RH (2008) Fatty acid interdigitation in stratum corneum model membranes: a neutron diffraction study. Eur Biophys J 37:759–771PubMedCrossRefGoogle Scholar
  18. 18.
    Grant CW, Mehlhorn IE, Florio E, Barber KR (1987) A long chain spin label for glycosphingolipid studies: transbilayer fatty acid interdigitation of lactosyl ceramide. Biochim Biophys Acta 902:169–177PubMedCrossRefGoogle Scholar
  19. 19.
    Boggs JM, Koshy KM (1994) Do the long fatty acid chains of sphingolipids interdigitate across the center of a bilayer of shorter chain symmetric phospholipids? Biochim Biophys Acta 1189:233–241PubMedCrossRefGoogle Scholar
  20. 20.
    Rintoul DA, Welti R (1989) Thermotropic behavior of mixtures of glycosphingolipids and phosphatidylcholine: effect of monovalent cations on sulfatide and galactosylceramide. Biochemistry 28:26–31PubMedCrossRefGoogle Scholar
  21. 21.
    Maggio B, Montich GG, Cumar FA (1988) Surface topography of sulfatide and gangliosides in unilamellar vesicles of dipalmitoylphosphatidylcholine. Chem Phys Lipids 46:137–146PubMedCrossRefGoogle Scholar
  22. 22.
    Wu X, Li QT (1999) Ca2+-induced fusion of sulfatide-containing phosphatidylethanolamine small unilamellar vesicles. J Lipid Res 40:1254–1262PubMedGoogle Scholar
  23. 23.
    Wu X, Li QT (1999) Hydration and stability of sulfatide-containing phosphatidylethanolamine small unilamellar vesicles. Biochim Biophys Acta 1416:285–294PubMedCrossRefGoogle Scholar
  24. 24.
    Wu X, Lee KH, Li QT (1996) Stability and pH sensitivity of sulfatide-containing phosphatidylethanolamine small unilamellar vesicles. Biochim Biophys Acta 1284:13–19PubMedCrossRefGoogle Scholar
  25. 25.
    Viani P, Cervato G, Gatti P, Cestaro B (1992) Calcitonin-induced changes in the organization of sulfatide-containing membranes. Biochim Biophys Acta 1106:77–84PubMedCrossRefGoogle Scholar
  26. 26.
    Bjorkqvist YJ, Nybond S, Nyholm TK, Slotte JP, Ramstedt B (2008) N-palmitoyl-sulfatide participates in lateral domain formation in complex lipid bilayers. Biochim Biophys Acta 1778:954–962PubMedCrossRefGoogle Scholar
  27. 27.
    Hao C, Sun R, Zhang J, Chang Y, Niu C (2009) Behavior of sulfatide/cholesterol mixed monolayers at the air/water interface. Colloids Surf B Biointerfaces 69:201–206PubMedCrossRefGoogle Scholar
  28. 28.
    Stewart RJ, Boggs JM (1990) Dependence of the surface expression of the glycolipid cerebroside sulfate on its lipid environment: comparison of sphingomyelin and phosphatidylcholine. Biochemistry 29:3644–3653PubMedCrossRefGoogle Scholar
  29. 29.
    Maggio B, Sturtevant JM, Yu RK (1987) Effect of myelin basic protein on the thermotropic behavior of aqueous dispersions of neutral and anionic glycosphingolipids and their mixtures with dipalmitoylphosphatidylcholine. J Biol Chem 262:2652–2659PubMedGoogle Scholar
  30. 30.
    Simons M, Nave KA (2015) Oligodendrocytes: myelination and axonal support. Cold Spring Harb Perspect Biol. doi: 10.1101/cshperspect.a020479 PubMedGoogle Scholar
  31. 31.
    Jessen KR, Mirsky R, Lloyd AC (2015) Schwann cells: development and role in nerve repair. Cold Spring Harb Perspect Biol 7(7):a020487. doi: 10.1101/cshperspect.a020487 PubMedCrossRefGoogle Scholar
  32. 32.
    Pernber Z, Molander-Melin M, Berthold CH, Hansson E, Fredman P (2002) Expression of the myelin and oligodendrocyte progenitor marker sulfatide in neurons and astrocytes of adult rat brain. J Neurosci Res 69:86–93PubMedCrossRefGoogle Scholar
  33. 33.
    Berntson Z, Hansson E, Ronnback L, Fredman P (1998) Intracellular sulfatide expression in a subpopulation of astrocytes in primary cultures. J Neurosci Res 52:559–568PubMedCrossRefGoogle Scholar
  34. 34.
    Isaac G, Pernber Z, Gieselmann V, Hansson E, Bergquist J, Mansson JE (2006) Sulfatide with short fatty acid dominates in astrocytes and neurons. FEBS J 273:1782–1790PubMedCrossRefGoogle Scholar
  35. 35.
    Yuki D, Sugiura Y, Zaima N, Akatsu H, Hashizume Y, Yamamoto T, Fujiwara M, Sugiyama K, Setou M (2011) Hydroxylated and non-hydroxylated sulfatide are distinctly distributed in the human cerebral cortex. Neuroscience 193:44–53PubMedCrossRefGoogle Scholar
  36. 36.
    De Haas CG, Lopes-Cardozo M (1995) Hydroxy- and non-hydroxy-galactolipids in developing rat CNS. Int J Dev Neurosci 13:447–454PubMedCrossRefGoogle Scholar
  37. 37.
    Pernber Z, Richter K, Mansson JE, Nygren H (2007) Sulfatide with different fatty acids has unique distributions in cerebellum as imaged by time-of-flight secondary ion mass spectrometry (TOF-SIMS). Biochim Biophys Acta 1771:202–209PubMedCrossRefGoogle Scholar
  38. 38.
    Pfeiffer SE, Warrington AE, Bansal R (1993) The oligodendrocyte and its many cellular processes. Trends Cell Biol 3:191–197PubMedCrossRefGoogle Scholar
  39. 39.
    Ishizuka I, Inomata M (1979) Sulphated glycoglycerolipids in rat brain: decrease and disappearance after developmental age. J Neurochem 33:387–388PubMedCrossRefGoogle Scholar
  40. 40.
    Raff MC, Mirsky R, Fields KL, Lisak RP, Dorfman SH, Silberberg DH, Gregson NA, Leibowitz S, Kennedy MC (1978) Galactocerebroside is a specific cell-surface antigenic marker for oligodendrocytes in culture. Nature 274:813–816PubMedGoogle Scholar
  41. 41.
    Hardy R, Reynolds R (1991) Proliferation and differentiation potential of rat forebrain oligodendroglial progenitors both in vitro and in vivo. Development 111:1061–1080PubMedGoogle Scholar
  42. 42.
    Poduslo SE, Miller K (1985) Levels of sulfatide synthesis distinguish oligodendroglia in different stages of maturation. Neurochem Res 10:1285–1297PubMedCrossRefGoogle Scholar
  43. 43.
    Bansal R, Warrington AE, Gard AL, Ranscht B, Pfeiffer SE (1989) Multiple and novel specificities of monoclonal antibodies O1, O4, and R-mAb used in the analysis of oligodendrocyte development. J Neurosci Res 24:548–557PubMedCrossRefGoogle Scholar
  44. 44.
    Dyer CA, Benjamins JA (1988) Antibody to galactocerebroside alters organization of oligodendroglial membrane sheets in culture. J Neurosci 8:4307–4318PubMedGoogle Scholar
  45. 45.
    Dyer CA, Benjamins JA (1989) Organization of oligodendroglial membrane sheets: II. Galactocerebroside:antibody interactions signal changes in cytoskeleton and myelin basic protein. J Neurosci Res 24:212–221PubMedCrossRefGoogle Scholar
  46. 46.
    Dyer CA, Benjamins JA (1990) Glycolipids and transmembrane signaling: antibodies to galactocerebroside cause an influx of calcium in oligodendrocytes. J Cell Biol 111:625–633PubMedCrossRefGoogle Scholar
  47. 47.
    Bansal R, Gard AL, Pfeiffer SE (1988) Stimulation of oligodendrocyte differentiation in culture by growth in the presence of a monoclonal antibody to sulfated glycolipid. J Neurosci Res 21:260–267PubMedCrossRefGoogle Scholar
  48. 48.
    Bansal R, Pfeiffer SE (1989) Reversible inhibition of oligodendrocyte progenitor differentiation by a monoclonal antibody against surface galactolipids. Proc Natl Acad Sci USA 86:6181–6185PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Bansal R, Winkler S, Bheddah S (1999) Negative regulation of oligodendrocyte differentiation by galactosphingolipids. J Neurosci 19:7913–7924PubMedGoogle Scholar
  50. 50.
    Owens GC, Bunge RP (1990) Schwann cells depleted of galactocerebroside express myelin-associated glycoprotein and initiate but do not continue the process of myelination. Glia 3:118–124PubMedCrossRefGoogle Scholar
  51. 51.
    Rosenbluth J, Moon D (2003) Dysmyelination induced in vitro by IgM antisulfatide and antigalactocerebroside monoclonal antibodies. J Neurosci Res 71:104–109PubMedCrossRefGoogle Scholar
  52. 52.
    Svennerholm L, Bostrom K, Jungbjer B (1997) Changes in weight and compositions of major membrane components of human brain during the span of adult human life of Swedes. Acta Neuropathol 94:345–352PubMedCrossRefGoogle Scholar
  53. 53.
    Crivello NA, Casseus SL, Peterson JW, Smith DE, Booth SL (2010) Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides. J Nutr Biochem 21:1083–1088PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Braak H, Braak E (1996) Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis. Acta Neuropathol 92:197–201PubMedCrossRefGoogle Scholar
  55. 55.
    Mitew S, Kirkcaldie MT, Halliday GM, Shepherd CE, Vickers JC, Dickson TC (2010) Focal demyelination in Alzheimer’s disease and transgenic mouse models. Acta Neuropathol 119:567–577PubMedCrossRefGoogle Scholar
  56. 56.
    Marbois BN, Faull KF, Fluharty AL, Raval-Fernandes S, Rome LH (2000) Analysis of sulfatide from rat cerebellum and multiple sclerosis white matter by negative ion electrospray mass spectrometry. Biochim Biophys Acta 1484:59–70PubMedCrossRefGoogle Scholar
  57. 57.
    Yahara S, Kawamura N, Kishimoto Y, Saida T, Tourtellotte WW (1982) A change in the cerebrosides and sulfatides in a demyelinating nervous system. Development of the methodology and study of multiple sclerosis and Wallerian degeneration. J Neurol Sci 54:303–315PubMedCrossRefGoogle Scholar
  58. 58.
    Moyano AL, Pituch K, Li G, van Breemen R, Mansson JE, Givogri MI (2013) Levels of plasma sulfatides C18: 0 and C24: 1 correlate with disease status in relapsing-remitting multiple sclerosis. J Neurochem 127:600–604PubMedCrossRefGoogle Scholar
  59. 59.
    Haghighi S, Lekman A, Nilsson S, Blomqvist M, Andersen O (2012) Myelin glycosphingolipid immunoreactivity and CSF levels in multiple sclerosis. Acta Neurol Scand 125:64–70PubMedCrossRefGoogle Scholar
  60. 60.
    Haghighi S, Lekman A, Nilsson S, Blomqvist M, Andersen O (2013) Increased CSF sulfatide levels and serum glycosphingolipid antibody levels in healthy siblings of multiple sclerosis patients. J Neurol Sci 326:35–39PubMedCrossRefGoogle Scholar
  61. 61.
    Halder RC, Jahng A, Maricic I, Kumar V (2007) Mini review: immune response to myelin-derived sulfatide and CNS-demyelination. Neurochem Res 32:257–262PubMedCrossRefGoogle Scholar
  62. 62.
    Jeon SB, Yoon HJ, Park SH, Kim IH, Park EJ (2008) Sulfatide, a major lipid component of myelin sheath, activates inflammatory responses as an endogenous stimulator in brain-resident immune cells. J Immunol 181:8077–8087PubMedCrossRefGoogle Scholar
  63. 63.
    Maricic I, Halder R, Bischof F, Kumar V (2014) Dendritic cells and anergic type I NKT cells play a crucial role in sulfatide-mediated immune regulation in experimental autoimmune encephalomyelitis. J Immunol 193:1035–1046PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Mycko MP, Sliwinska B, Cichalewska M, Cwiklinska H, Raine CS, Selmaj KW (2014) Brain glycolipids suppress T helper cells and inhibit autoimmune demyelination. J Neurosci 34:8646–8658PubMedCrossRefGoogle Scholar
  65. 65.
    Podbielska M, Hogan EL (2009) Molecular and immunogenic features of myelin lipids: incitants or modulators of multiple sclerosis? Mult Scler 15:1011–1029PubMedCrossRefGoogle Scholar
  66. 66.
    Ilyas AA, Chen ZW, Cook SD (2003) Antibodies to sulfatide in cerebrospinal fluid of patients with multiple sclerosis. J Neuroimmunol 139:76–80PubMedCrossRefGoogle Scholar
  67. 67.
    Don AS, Hsiao JH, Bleasel JM, Couttas TA, Halliday GM, Kim WS (2014) Altered lipid levels provide evidence for myelin dysfunction in multiple system atrophy. Acta Neuropathol Commun 2:150PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Schulte S, Stoffel W (1993) Ceramide UDPgalactosyltransferase from myelinating rat brain: purification, cloning, and expression. Proc Natl Acad Sci USA 90:10265–10269PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Stahl N, Jurevics H, Morell P, Suzuki K, Popko B (1994) Isolation, characterization, and expression of cDNA clones that encode rat UDP-galactose: ceramide galactosyltransferase. J Neurosci Res 38:234–242PubMedCrossRefGoogle Scholar
  70. 70.
    Coetzee T, Fujita N, Dupree J, Shi R, Blight A, Suzuki K, Popko B (1996) Myelination in the absence of galactocerebroside and sulfatide: normal structure with abnormal function and regional instability. Cell 86:209–219PubMedCrossRefGoogle Scholar
  71. 71.
    Saadat L, Dupree JL, Kilkus J, Han X, Traka M, Proia RL, Dawson G, Popko B (2010) Absence of oligodendroglial glucosylceramide synthesis does not result in CNS myelin abnormalities or alter the dysmyelinating phenotype of CGT-deficient mice. Glia 58:391–398PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Meixner M, Jungnickel J, Grothe C, Gieselmann V, Eckhardt M (2011) Myelination in the absence of UDP-galactose:ceramide galactosyl-transferase and fatty acid 2-hydroxylase. BMC Neurosci 12:22PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Dupree JL, Coetzee T, Suzuki K, Popko B (1998) Myelin abnormalities in mice deficient in galactocerebroside and sulfatide. J Neurocytol 27:649–659PubMedCrossRefGoogle Scholar
  74. 74.
    Bosio A, Binczek E, Haupt WF, Stoffel W (1998) Composition and biophysical properties of myelin lipid define the neurological defects in galactocerebroside- and sulfatide-deficient mice. J Neurochem 70:308–315PubMedCrossRefGoogle Scholar
  75. 75.
    Dupree JL, Suzuki K, Popko B (1998) Galactolipids in the formation and function of the myelin sheath. Microsc Res Tech 41:431–440PubMedCrossRefGoogle Scholar
  76. 76.
    Marcus J, Popko B (2002) Galactolipids are molecular determinants of myelin development and axo-glial organization. Biochim Biophys Acta 1573:406–413PubMedCrossRefGoogle Scholar
  77. 77.
    Dupree JL, Coetzee T, Blight A, Suzuki K, Popko B (1998) Myelin galactolipids are essential for proper node of Ranvier formation in the CNS. J Neurosci 18:1642–1649PubMedGoogle Scholar
  78. 78.
    Dupree JL, Popko B (1999) Genetic dissection of myelin galactolipid function. J Neurocytol 28:271–279PubMedCrossRefGoogle Scholar
  79. 79.
    Honke K, Hirahara Y, Dupree J, Suzuki K, Popko B, Fukushima K, Fukushima J, Nagasawa T, Yoshida N, Wada Y, Taniguchi N (2002) Paranodal junction formation and spermatogenesis require sulfoglycolipids. Proc Natl Acad Sci USA 99:4227–4232PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Wang C, Wang M, Zhou Y, Dupree JL, Han X (2014) Alterations in mouse brain lipidome after disruption of CST gene: a lipidomics study. Mol Neurobiol 50:88–96PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Marcus J, Honigbaum S, Shroff S, Honke K, Rosenbluth J, Dupree JL (2006) Sulfatide is essential for the maintenance of CNS myelin and axon structure. Glia 53:372–381PubMedCrossRefGoogle Scholar
  82. 82.
    Ishibashi T, Dupree JL, Ikenaka K, Hirahara Y, Honke K, Peles E, Popko B, Suzuki K, Nishino H, Baba H (2002) A myelin galactolipid, sulfatide, is essential for maintenance of ion channels on myelinated axon but not essential for initial cluster formation. J Neurosci 22:6507–6514PubMedGoogle Scholar
  83. 83.
    Hoshi T, Suzuki A, Hayashi S, Tohyama K, Hayashi A, Yamaguchi Y, Takeuchi K, Baba H (2007) Nodal protrusions, increased Schmidt-Lanterman incisures, and paranodal disorganization are characteristic features of sulfatide-deficient peripheral nerves. Glia 55:584–594PubMedCrossRefGoogle Scholar
  84. 84.
    Hayashi A, Kaneko N, Tomihira C, Baba H (2013) Sulfatide decrease in myelin influences formation of the paranodal axo-glial junction and conduction velocity in the sciatic nerve. Glia 61:466–474PubMedCrossRefGoogle Scholar
  85. 85.
    Marcus J, Dupree JL, Popko B (2000) Effects of galactolipid elimination on oligodendrocyte development and myelination. Glia 30:319–328PubMedCrossRefGoogle Scholar
  86. 86.
    Hirahara Y, Bansal R, Honke K, Ikenaka K, Wada Y (2004) Sulfatide is a negative regulator of oligodendrocyte differentiation: development in sulfatide-null mice. Glia 45:269–277PubMedCrossRefGoogle Scholar
  87. 87.
    Shroff SM, Pomicter AD, Chow WN, Fox MA, Colello RJ, Henderson SC, Dupree JL (2009) Adult CST-null mice maintain an increased number of oligodendrocytes. J Neurosci Res 87:3403–3414PubMedCrossRefGoogle Scholar
  88. 88.
    Kajigaya H, Tanaka KF, Hayashi A, Suzuki A, Ishibashi T, Ikenaka K, Baba H (2011) Increased numbers of oligodendrocyte lineage cells in the optic nerves of cerebroside sulfotransferase knockout mice. Proc Jpn Acad Ser B Phys Biol Sci 87:415–424PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Gielen E, Baron W, Vandeven M, Steels P, Hoekstra D, Ameloot M (2006) Rafts in oligodendrocytes: evidence and structure-function relationship. Glia 54:499–512PubMedCrossRefGoogle Scholar
  90. 90.
    Sonnino S, Prinetti A (2008) Membrane lipid domains and membrane lipid domain preparations: are they the same thing? Trends Glycosci Glycotechnol 20:315–340CrossRefGoogle Scholar
  91. 91.
    Kramer EM, Koch T, Niehaus A, Trotter J (1997) Oligodendrocytes direct glycosyl phosphatidylinositol-anchored proteins to the myelin sheath in glycosphingolipid-rich complexes. J Biol Chem 272:8937–8945PubMedCrossRefGoogle Scholar
  92. 92.
    Kramer EM, Klein C, Koch T, Boytinck M, Trotter J (1999) Compartmentation of Fyn kinase with glycosylphosphatidylinositol-anchored molecules in oligodendrocytes facilitates kinase activation during myelination. J Biol Chem 274:29042–29049PubMedCrossRefGoogle Scholar
  93. 93.
    Kim T, Pfeiffer SE (1999) Myelin glycosphingolipid/cholesterol-enriched microdomains selectively sequester the non-compact myelin proteins CNP and MOG. J Neurocytol 28:281–293PubMedCrossRefGoogle Scholar
  94. 94.
    Simons M, Kramer EM, Thiele C, Stoffel W, Trotter J (2000) Assembly of myelin by association of proteolipid protein with cholesterol- and galactosylceramide-rich membrane domains. J Cell Biol 151:143–154PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Taylor CM, Coetzee T, Pfeiffer SE (2002) Detergent-insoluble glycosphingolipid/cholesterol microdomains of the myelin membrane. J Neurochem 81:993–1004PubMedCrossRefGoogle Scholar
  96. 96.
    Marta CB, Taylor CM, Coetzee T, Kim T, Winkler S, Bansal R, Pfeiffer SE (2003) Antibody cross-linking of myelin oligodendrocyte glycoprotein leads to its rapid repartitioning into detergent-insoluble fractions, and altered protein phosphorylation and cell morphology. J Neurosci 23:5461–5471PubMedGoogle Scholar
  97. 97.
    Arvanitis DN, Min W, Gong Y, Heng YM, Boggs JM (2005) Two types of detergent-insoluble, glycosphingolipid/cholesterol-rich membrane domains from isolated myelin. J Neurochem 94:1696–1710PubMedCrossRefGoogle Scholar
  98. 98.
    Pomicter AD, Deloyht JM, Hackett AR, Purdie N, Sato-Bigbee C, Henderson SC, Dupree JL (2013) Nfasc155H and MAG are specifically susceptible to detergent extraction in the absence of the myelin sphingolipid sulfatide. Neurochem Res 38:2490–2502PubMedCrossRefGoogle Scholar
  99. 99.
    Ozgen H, Schrimpf W, Hendrix J, de Jonge JC, Lamb DC, Hoekstra D, Kahya N, Baron W (2014) The lateral membrane organization and dynamics of myelin proteins PLP and MBP are dictated by distinct galactolipids and the extracellular matrix. PLoS One 9:e101834PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Moyano AL, Li G, Lopez-Rosas A, Mansson JE, van Breemen RB, Givogri MI (2014) Distribution of C16:0, C18:0, C24:1, and C24:0 sulfatides in central nervous system lipid rafts by quantitative ultra-high-pressure liquid chromatography tandem mass spectrometry. Anal Biochem 467:31–39PubMedCrossRefGoogle Scholar
  101. 101.
    DeBruin LS, Haines JD, Bienzle D, Harauz G (2006) Partitioning of myelin basic protein into membrane microdomains in a spontaneously demyelinating mouse model for multiple sclerosis. Biochem Cell Biol 84:993–1005PubMedCrossRefGoogle Scholar
  102. 102.
    Debruin LS, Harauz G (2007) White matter rafting—membrane microdomains in myelin. Neurochem Res 32:213–228PubMedCrossRefGoogle Scholar
  103. 103.
    DeBruin LS, Haines JD, Wellhauser LA, Radeva G, Schonmann V, Bienzle D, Harauz G (2005) Developmental partitioning of myelin basic protein into membrane microdomains. J Neurosci Res 80:211–225PubMedCrossRefGoogle Scholar
  104. 104.
    Mehta NR, Lopez PH, Vyas AA, Schnaar RL (2007) Gangliosides and Nogo receptors independently mediate myelin-associated glycoprotein inhibition of neurite outgrowth in different nerve cells. J Biol Chem 282:27875–27886PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Pan B, Fromholt SE, Hess EJ, Crawford TO, Griffin JW, Sheikh KA, Schnaar RL (2005) Myelin-associated glycoprotein and complementary axonal ligands, gangliosides, mediate axon stability in the CNS and PNS: neuropathology and behavioral deficits in single- and double-null mice. Exp Neurol 195:208–217PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Schnaar RL, Lopez PH (2009) Myelin-associated glycoprotein and its axonal receptors. J Neurosci Res 87:3267–3276PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Vyas AA, Patel HV, Fromholt SE, Heffer-Lauc M, Vyas KA, Dang J, Schachner M, Schnaar RL (2002) Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration. Proc Natl Acad Sci USA 99:8412–8417PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Schafer DP, Bansal R, Hedstrom KL, Pfeiffer SE, Rasband MN (2004) Does paranode formation and maintenance require partitioning of neurofascin 155 into lipid rafts? J Neurosci 24:3176–3185PubMedCrossRefGoogle Scholar
  109. 109.
    Baron W, Bijlard M, Nomden A, de Jonge JC, Teunissen CE, Hoekstra D (2014) Sulfatide-mediated control of extracellular matrix-dependent oligodendrocyte maturation. Glia 62:927–942PubMedCrossRefGoogle Scholar
  110. 110.
    Brown MC, Besio Moreno M, Bongarzone ER, Cohen PD, Soto EF, Pasquini JM (1993) Vesicular transport of myelin proteolipid and cerebroside sulfates to the myelin membrane. J Neurosci Res 35:402–408PubMedCrossRefGoogle Scholar
  111. 111.
    Baron W, Ozgen H, Klunder B, de Jonge JC, Nomden A, Plat A, Trifilieff E, de Vries H, Hoekstra D (2015) The major myelin-resident protein PLP is transported to myelin membranes via a transcytotic mechanism: involvement of sulfatide. Mol Cell Biol 35(1):288–302PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Rodriguez M, Warrington AE, Pease LR (2009) Invited article: human natural autoantibodies in the treatment of neurologic disease. Neurology 72:1269–1276PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Warrington AE, Bieber AJ, Ciric B, Pease LR, Van Keulen V, Rodriguez M (2007) A recombinant human IgM promotes myelin repair after a single, very low dose. J Neurosci Res 85:967–976PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Sara Grassi
    • 1
  • Simona Prioni
    • 1
  • Livia Cabitta
    • 1
  • Massimo Aureli
    • 1
  • Sandro Sonnino
    • 1
  • Alessandro Prinetti
    • 1
  1. 1.Department of Medical Biotechnology and Translational MedicineUniversity of MilanSegrateItaly

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