The Enigmatic Role of Sulfatides: New Insights into Cellular Functions and Mechanisms of Protein Recognition

  • Shuyan Xiao
  • Carla V. Finkielstein
  • Daniel G. S. CapellutoEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 991)


Sulfatides are sphingolipids commonly found at the surface of most of eukaryotic cells. Sulfatides are not just structural components of the plasma membrane but also participate in a wide range of cellular processes including protein trafficking, cell adhesion and aggregation, axon-myelin interactions, neural plasticity, and immune responses, among others. The intriguing question is how can sulfatides trigger such cellular processes? Their dynamic presence and specific localization at plasma membrane sites may explain their multitasking role. Crystal and NMR structural studies have provided the basis for understanding the mechanism of binding by sulfatide-interacting proteins. These proteins generally exhibit a hydrophobic cavity that is responsible for the interaction with the sulfatide acyl chain, whereas the hydrophilic, negatively charged moiety can be found either buried in the hydrophobic cavity of the protein or exposed for additional intermolecular associations. Since sulfatides vary in their acyl chain composition, which are tissue-dependent, more emphasis on understanding acyl chain specificity by sulfatide-binding proteins is warranted. Importantly, changes in cellular sulfatide levels as well as circulating sulfatides in serum directly impact cardiovascular and cancer disease development and progress. Therefore, sulfatides might prove useful as novel biomarkers. The scope of this review is to overview cell functions and mechanisms of sulfatide recognition to better understand the role of these lipids in health and disease.


Sulfatides Ceramide Plasma membrane Sulfatide-binding proteins Platelet aggregation Disabled-2 Cluster of differentiation 1 



We thank Janet Webster for ­critical reading and comments on the manuscript. Work in the Capelluto laboratory is supported by the American Heart Association, the Thomas F. and Kate Miller Jeffress Memorial Trust, the National Science Foundation (IOS), and the National Institutes of Health (NICHD). C. V. Finkielstein’s research is funded by the National Science Foundation CAREER Award and by the Avon Foundation.


  1. 1.
    Adams JC, Lawler J (2011) The thrombospondins. CSH Perspect Biol 3(10):a009712Google Scholar
  2. 2.
    Ahn VE, Faull KF, Whitelegge JP, Fluharty AL, Prive GG (2003) Crystal structure of saposin B reveals a dimeric shell for lipid binding. Proc Natl Acad Sci USA 100:38–43PubMedGoogle Scholar
  3. 3.
    Alajlouni R, Drahos KE, Finkielstein CV, Capelluto DG (2011) Lipid-mediated membrane binding properties of Disabled-2. Biochim Biophys Acta 1808:2734–2744PubMedGoogle Scholar
  4. 4.
    Alderson NL, Rembiesa BM, Walla MD, Bielawska A, Bielawski J, Hama H (2004) The human FA2H gene encodes a fatty acid 2-hydroxylase. J Biol Chem 279:48562–48568PubMedGoogle Scholar
  5. 5.
    Andrews RK, Booth WJ, Bendall LJ, Berndt MC (1995) The amino Acid sequence glutamine-628 to valine-646 within the A1 repeat domain mediates binding of von Willebrand factor to bovine brain sulfatides and equine tendon collagen. Platelets 6:245–251PubMedGoogle Scholar
  6. 6.
    Barral DC, Brenner MB (2007) CD1 antigen presentation: how it works. Nat Rev Immunol 7:929–941PubMedGoogle Scholar
  7. 7.
    Bendelac A, Savage PB, Teyton L (2007) The biology of NKT cells. Annu Rev Immunol 25:297–336PubMedGoogle Scholar
  8. 8.
    Blomqvist M, Rhost S, Teneberg S, Lofbom L, Osterbye T, Brigl M, Mansson JE, Cardell SL (2009) Multiple tissue-specific isoforms of sulfatide activate CD1d-restricted type II NKT cells. Eur J Immunol 39:1726–1735PubMedGoogle Scholar
  9. 9.
    Borthakur G, Cruz MA, Dong JF, McIntire L, Li F, Lopez JA, Thiagarajan P (2003) Sulfatides inhibit platelet adhesion to von Willebrand factor in flowing blood. J Thromb Haemost 1:1288–1295PubMedGoogle Scholar
  10. 10.
    Bruun JM, Roeske-Nielsen A, Richelsen B, Fredman P, Buschard K (2007) Sulfatide increases adiponectin and decreases TNF-alpha, IL-6, and IL-8 in human adipose tissue in vitro. Mol Cell Endocrinol 263:142–148PubMedGoogle Scholar
  11. 11.
    Calderon RO, Attema B, DeVries GH (1995) Lipid composition of neuronal cell bodies and neurites from cultured dorsal root ganglia. J Neurochem 64:424–429PubMedGoogle Scholar
  12. 12.
    Chen M, Geng JG (2006) P-selectin mediates adhesion of leukocytes, platelets, and cancer cells in inflammation, thrombosis, and cancer growth and metastasis. Arch Immunol Ther Exp (Warsz) 54:75–84Google Scholar
  13. 13.
    Chi S, Qi Z (2006) Regulatory effect of sulphatides on BKCa channels. Br J Pharmacol 149:1031–1038PubMedGoogle Scholar
  14. 14.
    Choi BK, Schifferli DM (1999) Lysine residue 117 of the FasG adhesin of enterotoxigenic Escherichia coli is essential for binding of 987P fimbriae to sulfatide. Infect Immun 67:5755–5761PubMedGoogle Scholar
  15. 15.
    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 86:209–219PubMedGoogle Scholar
  16. 16.
    D’Hooge R, Van Dam D, Franck F, Gieselmann V, De Deyn PP (2001) Hyperactivity, neuromotor defects, and impaired learning and memory in a mouse model for metachromatic leukodystrophy. Brain Res 907:35–43PubMedGoogle Scholar
  17. 17.
    De Libero G, Mori L (2012) Novel insights into lipid antigen presentation. Trends Immunol 33:103–111PubMedGoogle Scholar
  18. 18.
    Drahos KE, Welsh JD, Finkielstein CV, Capelluto DG (2009) Sulfatides partition disabled-2 in response to platelet activation. PLoS One 4:e8007PubMedGoogle Scholar
  19. 19.
    Dupree JL, Coetzee T, Suzuki K, Popko B (1998) Myelin abnormalities in mice deficient in galactocerebroside and sulfatide. J Neurocytol 27:649–659PubMedGoogle Scholar
  20. 20.
    Eckhardt M (2008) The role and metabolism of sulfatide in the nervous system. Mol Neurobiol 37:93–103PubMedGoogle Scholar
  21. 21.
    Eckhardt M, Hedayati KK, Pitsch J, Lullmann-Rauch R, Beck H, Fewou SN, Gieselmann V (2007) Sulfatide storage in neurons causes hyperexcitability and axonal degeneration in a mouse model of metachromatic leukodystrophy. J Neurosci 27:9009–9021PubMedGoogle Scholar
  22. 22.
    Fantini J, Hammache D, Delezay O, Pieroni G, Tamalet C, Yahi N (1998) Sulfatide inhibits HIV-1 entry into CD4-/CXCR4+ cells. Virology 246:211–220PubMedGoogle Scholar
  23. 23.
    Fredman P, Mansson JE, Rynmark BM, Josefsen K, Ekblond A, Halldner L, Osterbye T, Horn T, Buschard K (2000) The glycosphingolipid sulfatide in the islets of Langerhans in rat pancreas is processed through recycling: possible involvement in insulin trafficking. Glycobiology 10:39–50PubMedGoogle Scholar
  24. 24.
    Frenette PS, Johnson RC, Hynes RO, Wagner DD (1995) Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin. Proc Natl Acad Sci U S A 92:7450–7454PubMedGoogle Scholar
  25. 25.
    Frenette PS, Moyna C, Hartwell DW, Lowe JB, Hynes RO, Wagner DD (1998) Platelet-endothelial interactions in inflamed mesenteric venules. Blood 91:1318–1324PubMedGoogle Scholar
  26. 26.
    Frenette PS, Wagner DD (1996) Adhesion molecules–Part 1. N Engl J Med 334(23):1526–1529PubMedGoogle Scholar
  27. 27.
    Frenette PS, Wagner DD (1996) Adhesion molecules–Part II: blood vessels and blood cells. N Engl J Med 335:43–45PubMedGoogle Scholar
  28. 28.
    Gahmberg CG (1997) Leukocyte adhesion: CD11/CD18 integrins and intercellular adhesion molecules. Curr Opin Cell Biol 9:643–650PubMedGoogle Scholar
  29. 29.
    Gnewuch C, Jaques G, Havemann K, Wiegandt H (1994) Re-assessment of acidic glycosphingolipids in small-cell-lung-cancer tissues and cell lines. Int J Cancer 8:125–126Google Scholar
  30. 30.
    Goncalves C, Berthiaume F, Mourez M, Dubreuil JD (2008) Escherichia coli STb toxin binding to sulfatide and its inhibition by carragenan. FEMS Microbiol Lett 281:30–35PubMedGoogle Scholar
  31. 31.
    Guchhait P, Shrimpton CN, Honke K, Rumbaut RE, Lopez JA, Thiagarajan P (2008) Effect of an anti-sulfatide single-chain antibody probe on platelet function. Thromb Haemost 99:552–557PubMedGoogle Scholar
  32. 32.
    Guo NH, Krutzsch HC, Negre E, Vogel T, Blake DA, Roberts DD (1992) Heparin- and sulfatide-binding peptides from the type I repeats of human thrombospondin promote melanoma cell adhesion. Proc Natl Acad Sci U S A 89:3040–3044PubMedGoogle Scholar
  33. 33.
    Halder RC, Jahng A, Maricic I, Kumar V (2007) Mini review: immune response to myelin-derived sulfatide and CNS-demyelination. Neurochem Res 32:257–262PubMedGoogle Scholar
  34. 34.
    Harrison D, Hussain SA, Combs AC, Ervasti JM, Yurchenco PD, Hohenester E (2007) Crystal structure and cell surface anchorage sites of laminin alpha1LG4-5. J Biol Chem 282:11573–11581PubMedGoogle Scholar
  35. 35.
    Hirahara Y, Tsuda M, Wada Y, Honke K (2000) cDNA cloning, genomic cloning, and tissue-specific regulation of mouse cerebroside sulfotransferase. Eur J Biochem 267:1909–1917PubMedGoogle Scholar
  36. 36.
    Hiraiwa N, Fukuda Y, Imura H, Tadano-Aritomi K, Nagai K, Ishizuka I, Kannagi R (1990) Accumulation of highly acidic sulfated glycosphingolipids in human hepatocellular carcinoma defined by a series of monoclonal antibodies. Cancer Res 50:2917–2928PubMedGoogle Scholar
  37. 37.
    Hohenester E, Tisi D, Talts JF, Timpl R (1999) The crystal structure of a laminin G-like module reveals the molecular basis of alpha-dystroglycan binding to laminins, perlecan, and agrin. Mol Cell 4:783–792PubMedGoogle Scholar
  38. 38.
    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(7):4227–4232. doi: 10.1073/pnas.032068299 PubMedGoogle Scholar
  39. 39.
    Honke K, Zhang Y, Cheng X, Kotani N, Taniguchi N (2004) Biological roles of sulfoglycolipids and pathophysiology of their deficiency. Glycoconj J 21:59–62PubMedGoogle Scholar
  40. 40.
    Hu R, Li G, Kamijo Y, Aoyama T, Nakajima T, Inoue T, Node K, Kannagi R, Kyogashima M, Hara A (2007) Serum sulfatides as a novel biomarker for cardiovascular disease in patients with end-stage renal failure. Glycoconj J 24:565–571PubMedGoogle Scholar
  41. 41.
    Huang CL, Cheng JC, Liao CH, Stern A, Hsieh JT, Wang CH, Hsu HL, Tseng CP (2004) Disabled-2 is a negative regulator of integrin alpha(IIb)beta(3)-mediated fibrinogen adhesion and cell signaling. J Biol Chem 279:42279–42289PubMedGoogle Scholar
  42. 42.
    Huang CL, Cheng JC, Stern A, Hsieh JT, Liao CH, Tseng CP (2006) Disabled-2 is a novel alphaIIb-integrin-binding protein that negatively regulates platelet-fibrinogen interactions and platelet aggregation. J Cell Sci 119:4420–4430PubMedGoogle Scholar
  43. 43.
    Huesca M, Borgia S, Hoffman P, Lingwood CA (1996) Acidic pH changes receptor binding specificity of Helicobacter pylori: a binary adhesion model in which surface heat shock (stress) proteins mediate sulfatide recognition in gastric colonization. Infect Immun 64:2643–2648PubMedGoogle Scholar
  44. 44.
    Huesca M, Goodwin A, Bhagwansingh A, Hoffman P, Lingwood CA (1998) Characterization of an acidic-pH-inducible stress protein (hsp70), a putative sulfatide binding adhesin, from Helicobacter pylori. Infect Immun 66(9):4061–4067PubMedGoogle Scholar
  45. 45.
    Inoue T, Taguchi I, Abe S, Li G, Hu R, Nakajima T, Hara A, Aoyama T, Kannagi R, Kyogashima M, Node K (2010) Sulfatides are associated with neointimal thickening after vascular injury. Atherosclerosis 211(1):291–296PubMedGoogle Scholar
  46. 46.
    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 273:1782–1790PubMedGoogle Scholar
  47. 47.
    Ishizuka I (1997) Chemistry and functional distribution of sulfoglycolipids. Prog Lipid Res 36(4):245–319PubMedGoogle Scholar
  48. 48.
    Iwamura C, Shinoda K, Endo Y, Watanabe Y, Tumes DJ, Motohashi S, Kawahara K, Kinjo Y, Nakayama T (2012) Regulation of memory CD4 T-cell pool size and function by natural killer T cells in vivo. Proc Natl Acad Sci U S A 109:16992–16997PubMedGoogle Scholar
  49. 49.
    Jackson SP (2007) The growing complexity of platelet aggregation. Blood 109:5087–5095PubMedGoogle Scholar
  50. 50.
    Jahng A, Maricic I, Aguilera C, Cardell S, Halder RC, Kumar V (2004) Prevention of autoimmunity by targeting a distinct, noninvariant CD1d-reactive T cell population reactive to sulfatide. J Exp Med 199:947–957PubMedGoogle Scholar
  51. 51.
    Jansson L, Tobias J, Jarefjall C, Lebens M, Svennerholm AM, Teneberg S (2009) Sulfatide recognition by colonization factor antigen CS6 from enterotoxigenic Escherichia coli. PLoS One 4:e4487PubMedGoogle Scholar
  52. 52.
    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 181:8077–8087PubMedGoogle Scholar
  53. 53.
    Kalb E, Engel J (1991) Binding and calcium-induced aggregation of laminin onto lipid bilayers. J Biol Chem 266:19047–19052PubMedGoogle Scholar
  54. 54.
    Kamlekar RK, Gao Y, Kenoth R, Molotkovsky JG, Prendergast FG, Malinina L, Patel DJ, Wessels WS, Venyaminov SY, Brown RE (2010) Human GLTP: three distinct functions for the three tryptophans in a novel peripheral amphitropic fold. Biophys J 99:2626–2635PubMedGoogle Scholar
  55. 55.
    Kanter JL, Narayana S, Ho PP, Catz I, Warren KG, Sobel RA, Steinman L, Robinson WH (2006) Lipid microarrays identify key mediators of autoimmune brain inflammation. Nat Med 12:138–143PubMedGoogle Scholar
  56. 56.
    Kolter T, Sandhoff K (2005) Principles of lysosomal membrane digestion: stimulation of sphingolipid degradation by sphingolipid activator proteins and anionic lysosomal lipids. Annu Rev Cell Dev Biol 21:81–103PubMedGoogle Scholar
  57. 57.
    Kushi Y, Arita M, Ishizuka I, Kasama T, Fredman P, Handa S (1996) Sulfatide is expressed in both erythrocytes and platelets of bovine origin. Biochim Biophys Acta 1304(3):254–262PubMedGoogle Scholar
  58. 58.
    Kwiatkowska K (2010) One lipid, multiple functions: how various pools of PI(4,5)P(2) are created in the plasma membrane. Cell Mol Life Sci 67:3927–3946PubMedGoogle Scholar
  59. 59.
    Kyogashima M (2004) The role of sulfatide in thrombogenesis and haemostasis. Arch Biochem Biophys 426:157–162PubMedGoogle Scholar
  60. 60.
    Larsen E, Celi A, Gilbert GE, Furie BC, Erban JK, Bonfanti R, Wagner DD, Furie B (1989) PADGEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes. Cell 59:305–312PubMedGoogle Scholar
  61. 61.
    Li J, Pearl DK, Pfeiffer SE, Yates AJ (1994) Patterns of reactivity with anti-glycolipid antibodies in human primary brain tumors. J Neurosci Res 39:148–158PubMedGoogle Scholar
  62. 62.
    Liu Y, Chen Y, Momin A, Shaner R, Wang E, Bowen NJ, Matyunina LV, Walker LD, McDonald JF, Sullards MC, Merrill AH Jr (2010) Elevation of sulfatides in ovarian cancer: an integrated transcriptomic and lipidomic analysis including tissue-imaging mass spectrometry. Mol Cancer 9:186PubMedGoogle Scholar
  63. 63.
    Makhlouf AM, Fathalla MM, Zakhary MA, Makarem MH (2004) Sulfatides in ovarian tumors: clinicopathological correlates. Int J Gynecol Cancer 14:89–93PubMedGoogle Scholar
  64. 64.
    Malinina L, Malakhova ML, Kanack AT, Lu M, Abagyan R, Brown RE, Patel DJ (2006) The liganding of glycolipid transfer protein is controlled by glycolipid acyl structure. PLoS Biol 4:e362PubMedGoogle Scholar
  65. 65.
    Malinina L, Malakhova ML, Teplov A, Brown RE, Patel DJ (2004) Structural basis for glycosphingolipid transfer specificity. Nature 430:1048–1053PubMedGoogle Scholar
  66. 66.
    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 53:372–381PubMedGoogle Scholar
  67. 67.
    Matsushita T, Meyer D, Sadler JE (2000) Localization of von willebrand factor-binding sites for platelet glycoprotein Ib and botrocetin by charged-to-alanine scanning mutagenesis. J Biol Chem 275:11044–11049PubMedGoogle Scholar
  68. 68.
    Mattjus P (2009) Glycolipid transfer proteins and membrane interaction. Biochim Biophys Acta 1788:267–272PubMedGoogle Scholar
  69. 69.
    Matyas GR, Beck Z, Karasavvas N, Alving CR (2009) Lipid binding properties of 4E10, 2F5, and WR304 monoclonal antibodies that neutralize HIV-1. Biochim Biophys Acta 1788:660–665PubMedGoogle Scholar
  70. 70.
    Merten M, Beythien C, Gutensohn K, Kuhnl P, Meinertz T, Thiagarajan P (2005) Sulfatides activate platelets through P-selectin and enhance platelet and platelet-leukocyte aggregation. Arterioscler Thromb Vasc Biol 25:258–263PubMedGoogle Scholar
  71. 71.
    Merten M, Thiagarajan P (2000) P-selectin expression on platelets determines size and stability of platelet aggregates. Circulation 102:1931–1936PubMedGoogle Scholar
  72. 72.
    Merten M, Thiagarajan P (2001) Role for sulfatides in platelet aggregation. Circulation 104:2955–2960PubMedGoogle Scholar
  73. 73.
    Moody DB, Zajonc DM, Wilson IA (2005) Anatomy of CD1-lipid antigen complexes. Nat Rev Immunol 5:387–399PubMedGoogle Scholar
  74. 74.
    Morichika H, Hamanaka Y, Tai T, Ishizuka I (1996) Sulfatides as a predictive factor of lymph node metastasis in patients with colorectal adenocarcinoma. Cancer 78(1):43–47PubMedGoogle Scholar
  75. 75.
    Nakajima T, Kamijo Y, Yuzhe H, Kimura T, Tanaka N, Sugiyama E, Nakamura K, Kyogashima M, Hara A, Aoyama T (2013) Peroxisome proliferator-activated receptor alpha mediates enhancement of gene expression of cerebroside sulfotransferase in several murine organs. Glycoconj J in pressGoogle Scholar
  76. 76.
    Nakayama T, Matsushita T, Yamamoto K, Mutsuga N, Kojima T, Katsumi A, Nakao N, Sadler JE, Naoe T, Saito H (2008) Identification of amino acid residues responsible for von Willebrand factor binding to sulfatide by charged-to-alanine-scanning mutagenesis. Int J Hematol 87:363–370PubMedGoogle Scholar
  77. 77.
    Norton WT, Autilio LA (1965) The chemical composition of bovine CNS myelin. Ann N Y Acad Sci 122:77–85PubMedGoogle Scholar
  78. 78.
    Patel O, Pellicci DG, Gras S, Sandoval-Romero ML, Uldrich AP, Mallevaey T, Clarke AJ, Le Nours J, Theodossis A, Cardell SL, Gapin L, Godfrey DI, Rossjohn J (2012) Recognition of CD1d-sulfatide mediated by a type II natural killer T cell antigen receptor. Nat Immunol 13:857–863PubMedGoogle Scholar
  79. 79.
    Peng L, Suzuki K (1987) Ultrastructural study of neurons in metachromatic leukodystrophy. Clin Neuropathol 6:224–230PubMedGoogle Scholar
  80. 80.
    Perino J, Foo CH, Spehner D, Cohen GH, Eisenberg RJ, Crance JM, Favier AL (2011) Role of sulfatide in vaccinia virus infection. Biol Cell 103:319–331PubMedGoogle Scholar
  81. 81.
    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 69:86–93PubMedGoogle Scholar
  82. 82.
    Plow EF, Pierschbacher MD, Ruoslahti E, Marguerie GA, Ginsberg MH (1985) The effect of Arg-Gly-Asp-containing peptides on fibrinogen and von Willebrand factor binding to platelets. Proc Natl Acad Sci U S A 82:8057–8061PubMedGoogle Scholar
  83. 83.
    Pouyani T, Seed B (1995) PSGL-1 recognition of P-selectin is controlled by a tyrosine sulfation consensus at the PSGL-1 amino terminus. Cell 83:333–343PubMedGoogle Scholar
  84. 84.
    Ramakrishnan H, Hedayati KK, Lullmann-Rauch R, Wessig C, Fewou SN, Maier H, Goebel HH, Gieselmann V, Eckhardt M (2007) Increasing sulfatide synthesis in myelin-forming cells of arylsulfatase A-deficient mice causes demyelination and neurological symptoms reminiscent of human metachromatic leukodystrophy. J Neurosci 27:9482–9490PubMedGoogle Scholar
  85. 85.
    Roberts DD, Haverstick DM, Dixit VM, Frazier WA, Santoro SA, Ginsburg V (1985) The platelet glycoprotein thrombospondin binds specifically to sulfated glycolipids. J Biol Chem 260:9405–9411PubMedGoogle Scholar
  86. 86.
    Roberts DD, Rao CN, Liotta LA, Gralnick HR, Ginsburg V (1986) Comparison of the specificities of laminin, thrombospondin, and von Willebrand factor for binding to sulfated glycolipids. J Biol Chem 261:6872–6877PubMedGoogle Scholar
  87. 87.
    Roeske-Nielsen A, Fredman P, Mansson JE, Bendtzen K, Buschard K (2004) Beta-galactosylceramide increases and sulfatide decreases cytokine and chemokine production in whole blood cells. Immunol Lett 91:205–211PubMedGoogle Scholar
  88. 88.
    Romo GM, Dong JF, Schade AJ, Gardiner EE, Kansas GS, Li CQ, McIntire LV, Berndt MC, Lopez JA (1999) The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin. J Exp Med 190:803–814PubMedGoogle Scholar
  89. 89.
    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 58:391–398PubMedGoogle Scholar
  90. 90.
    Sakakibara N, Gasa S, Kamio K, Makita A, Nonomura K, Togashi M, Koyanagi T, Hatae Y, Takeda K (1991) Distinctive glycolipid patterns in Wilms’ tumor and renal cell carcinoma. Cancer Lett 57:187–192PubMedGoogle Scholar
  91. 91.
    Samygina VR, Popov AN, Cabo-Bilbao A, Ochoa-Lizarralde B, Goni-de-Cerio F, Zhai X, Molotkovsky JG, Patel DJ, Brown RE, Malinina L (2011) Enhanced selectivity for sulfatide by engineered human glycolipid transfer protein. Structure 19:1644–1654PubMedGoogle Scholar
  92. 92.
    Sandhoff R, Grieshaber H, Djafarzadeh R, Sijmonsma TP, Proudfoot AE, Handel TM, Wiegandt H, Nelson PJ, Grone HJ (2005) Chemokines bind to sulfatides as revealed by surface plasmon resonance. Biochim Biophys Acta 1687:52–63PubMedGoogle Scholar
  93. 93.
    Sarlieve LL, Zalc B, Neskovic NM, Zanetta JP, Rebel G (1984) Structure and immunological localization of spleen sulfolipid. Biochim Biophys Acta 795:166–168PubMedGoogle Scholar
  94. 94.
    Shamshiev A, Gober HJ, Donda A, Mazorra Z, Mori L, De Libero G (2002) Presentation of the same glycolipid by different CD1 molecules. J Exp Med 195:1013–1021PubMedGoogle Scholar
  95. 95.
    Shimazawa M, Kondo K, Hara H, Nakashima M, Umemura K (2005) Sulfatides, L- and P-selectin ligands, exacerbate the intimal hyperplasia occurring after endothelial injury. Eur J Pharmacol 520:118–126PubMedGoogle Scholar
  96. 96.
    Simonis D, Schlesinger M, Seelandt C, Borsig L, Bendas G (2010) Analysis of SM4 sulfatide as a P-selectin ligand using model membranes. Biophys Chem 150:98–104PubMedGoogle Scholar
  97. 97.
    Sugiyama T, Miyazawa M, Mikami M, Goto Y, Nishijima Y, Ikeda M, Hirasawa T, Muramatsu T, Takekoshi S, Iwamori M (2012) Enhanced expression of sulfatide, a sulfated glycolipid, in well-differentiated endometrial adenocarcinoma. Int J Gynecol Cancer 22:1192–1197PubMedGoogle Scholar
  98. 98.
    Sundell IB, Halder R, Zhang M, Maricic I, Koka PS, Kumar V (2010) Sulfatide administration leads to inhibition of HIV-1 replication and enhanced hematopoeisis. J Stem Cells 5:33–42PubMedGoogle Scholar
  99. 99.
    Suzuki T, Sometani A, Yamazaki Y, Horiike G, Mizutani Y, Masuda H, Yamada M, Tahara H, Xu G, Miyamoto D, Oku N, Okada S, Kiso M, Hasegawa A, Ito T, Kawaoka Y, Suzuki Y (1996) Sulphatide binds to human and animal influenza A viruses, and inhibits the viral infection. Biochem J 318:389–393PubMedGoogle Scholar
  100. 100.
    Svennerholm L, Bostrom K, Fredman P, Jungbjer B, Mansson JE, Rynmark BM (1992) Membrane lipids of human peripheral nerve and spinal cord. Biochim Biophys Acta 1128:1–7PubMedGoogle Scholar
  101. 101.
    Takahashi T, Murakami K, Nagakura M, Kishita H, Watanabe S, Honke K, Ogura K, Tai T, Kawasaki K, Miyamoto D, Hidari KI, Guo CT, Suzuki Y, Suzuki T (2008) Sulfatide is required for efficient replication of influenza A virus. J Virol 82:5940–5950PubMedGoogle Scholar
  102. 102.
    Talts JF, Andac Z, Gohring W, Brancaccio A, Timpl R (1999) Binding of the G domains of laminin alpha1 and alpha2 chains and perlecan to heparin, sulfatides, alpha-dystroglycan and several extracellular matrix proteins. EMBO J 18:863–870PubMedGoogle Scholar
  103. 103.
    Taraboletti G, Rao CN, Krutzsch HC, Liotta LA, Roberts DD (1990) Sulfatide-binding domain of the laminin A chain. J Biol Chem 265:12253–12258PubMedGoogle Scholar
  104. 104.
    Theilmeier G, Lenaerts T, Remacle C, Collen D, Vermylen J, Hoylaerts MF (1999) Circulating activated platelets assist THP-1 monocytoid/endothelial cell interaction under shear stress. Blood 94:2725–2734PubMedGoogle Scholar
  105. 105.
    Thudichum JL (1884) A treatise on the chemical constitution of the brain. Balliere, Tindall, and Cox, LondonGoogle Scholar
  106. 106.
    Tjong SC, Wu PL, Wang CM, Huang WN, Ho NL, Wu WG (2007) Role of glycosphingolipid conformational change in membrane pore forming activity of cobra cardiotoxin. Biochemistry 46:12111–12123PubMedGoogle Scholar
  107. 107.
    van Zyl R, Gieselmann V, Eckhardt M (2010) Elevated sulfatide levels in neurons cause lethal audiogenic seizures in mice. J Neurochem 112:282–295PubMedGoogle Scholar
  108. 108.
    Vargas ME, Watanabe J, Singh SJ, Robinson WH, Barres BA (2010) Endogenous antibodies promote rapid myelin clearance and effective axon regeneration after nerve injury. Proc Natl Acad Sci USA 107:11993–11998PubMedGoogle Scholar
  109. 109.
    Vos JP, Lopes-Cardozo M, Gadella BM (1994) Metabolic and functional aspects of sulfogalactolipids. Biochim Biophys Acta 1211:125–149PubMedGoogle Scholar
  110. 110.
    Wang CH, Liu JH, Lee SC, Hsiao CD, Wu WG (2006) Glycosphingolipid-facilitated membrane insertion and internalization of cobra cardiotoxin. The sulfatide.cardiotoxin complex structure in a membrane-like environment suggests a lipid-dependent cell-penetrating mechanism for membrane binding polypeptides. J Biol Chem 281:656–667PubMedGoogle Scholar
  111. 111.
    Wang L, Kamijo Y, Matsumoto A, Nakajima T, Higuchi M, Kannagi R, Kyogashima M, Aoyama T, Hara A (2011) Kidney transplantation recovers the reduction level of serum sulfatide in ESRD patients via processes correlated to oxidative stress and platelet count. Glycoconj J 28:125–135PubMedGoogle Scholar
  112. 112.
    Watarai S, Onuma M, Yamamoto S, Yasuda T (1990) Inhibitory effect of liposomes containing sulfatide or cholesterol sulfate on syncytium formation induced by bovine immunodeficiency virus-infected cells. J Biochem 108:507–509PubMedGoogle Scholar
  113. 113.
    Welsh JD, Charonko JJ, Salmanzadeh A, Drahos KE, Shafiee H, Stremler MA, Davalos RV, Capelluto DG, Vlachos PP, Finkielstein CV (2011) Disabled-2 modulates homotypic and heterotypic platelet interactions by binding to sulfatides. Br J Haematol 154:122–133PubMedGoogle Scholar
  114. 114.
    Winzeler AM, Mandemakers WJ, Sun MZ, Stafford M, Phillips CT, Barres BA (2011) The lipid sulfatide is a novel myelin-associated inhibitor of CNS axon outgrowth. J Neurosci 31:6481–6492PubMedGoogle Scholar
  115. 115.
    Wu PL, Chiu CR, Huang WN, Wu WG (2012) The role of sulfatide lipid domains in the membrane pore-forming activity of cobra cardiotoxin. Biochim Biophys Acta 1818:1378–1385PubMedGoogle Scholar
  116. 116.
    Xiao S, Charonko JJ, Fu X, Salmanzadeh A, Davalos RV, Vlachos PP, Finkielstein CV, Capelluto DG (2012) Structure, sulfatide binding properties, and inhibition of platelet aggregation by a Disabled-2 protein-derived peptide. J Biol Chem 287:37691–37702PubMedGoogle Scholar
  117. 117.
    Yaghootfam A, Sorkalla T, Haberlein H, Gieselmann V, Kappler J, Eckhardt M (2007) Cerebroside sulfotransferase forms homodimers in living cells. Biochemistry 46:9260–9269PubMedGoogle Scholar
  118. 118.
    Yang H, Lang S, Zhai Z, Li L, Kahr WH, Chen P, Brkic J, Spring CM, Flick MJ, Degen JL, Freedman J, Ni H (2009) Fibrinogen is required for maintenance of platelet intracellular and cell-surface P-selectin expression. Blood 114:425–436PubMedGoogle Scholar
  119. 119.
    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 193:44–53PubMedGoogle Scholar
  120. 120.
    Zajonc DM, Elsliger MA, Teyton L, Wilson IA (2003) Crystal structure of CD1a in complex with a sulfatide self antigen at a resolution of 2.15 A. Nat Immunol 4:808–815PubMedGoogle Scholar
  121. 121.
    Zajonc DM, Maricic I, Wu D, Halder R, Roy K, Wong CH, Kumar V, Wilson IA (2005) Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity. J Exp Med 202:1517–1526PubMedGoogle Scholar
  122. 122.
    Zeng Z, Castano AR, Segelke BW, Stura EA, Peterson PA, Wilson IA (1997) Crystal structure of mouse CD1: an MHC-like fold with a large hydrophobic binding groove. Science 277:339–345PubMedGoogle Scholar
  123. 123.
    Zhang X, Nakajima T, Kamijo Y, Li G, Hu R, Kannagi R, Kyogashima M, Aoyama T, Hara A (2009) Acute kidney injury induced by protein-overload nephropathy down-regulates gene expression of hepatic cerebroside sulfotransferase in mice, resulting in reduction of liver and serum sulfatides. Biochem Biophys Res Commun 390:1382–1388PubMedGoogle Scholar
  124. 124.
    Zhang XL, Rafi MA, DeGala G, Wenger DA (1990) Insertion in the mRNA of a metachromatic leukodystrophy patient with sphingolipid activator protein-1 deficiency. Proc Natl Acad Sci USA 87:1426–1430PubMedGoogle Scholar
  125. 125.
    Zhou Z, Thiagarajan P, Udden M, Lopez JA, Guchhait P (2011) Erythrocyte membrane sulfatide plays a crucial role in the adhesion of sickle erythrocytes to endothelium. Thromb Haemost 105:1046–1052PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Shuyan Xiao
    • 1
  • Carla V. Finkielstein
    • 2
  • Daniel G. S. Capelluto
    • 1
    Email author
  1. 1.Protein Signaling Domains Laboratory, Department of Biological SciencesVirginia TechBlacksburgUSA
  2. 2.Integrated Cellular Responses Laboratory, Department of Biological SciencesVirginia TechBlacksburgUSA

Personalised recommendations