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Functions of lipid raft membrane microdomains at the blood–brain barrier

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Abstract

The blood–brain barrier (BBB) is a highly specialized structural and functional component of the central nervous system that separates the circulating blood from the brain and spinal cord parenchyma. Brain endothelial cells (BECs) that primarily constitute the BBB are tightly interconnected by multiprotein complexes, the adherens junctions and the tight junctions, thereby creating a highly restrictive cellular barrier. Lipid-enriched membrane microdomain compartmentalization is an inherent property of BECs and allows for the apicobasal polarity of brain endothelium, temporal and spatial coordination of cell signaling events, and actin remodeling. In this manuscript, we review the role of membrane microdomains, in particular lipid rafts, in the BBB under physiological conditions and during leukocyte transmigration/diapedesis. Furthermore, we propose a classification of endothelial membrane microdomains based on their function, or at least on the function ascribed to the molecules included in such heterogeneous rafts: (1) rafts associated with interendothelial junctions and adhesion of BECs to basal lamina (scaffolding rafts); (2) rafts involved in immune cell adhesion and migration across brain endothelium (adhesion rafts); (3) rafts associated with transendothelial transport of nutrients and ions (transporter rafts).

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References

  1. Reese TS, Karnovsky MJ (1967) Fine structural localization of a blood–brain barrier to exogenous peroxidase. J Cell Biol 1:207–217

    Article  Google Scholar 

  2. Brightman MW, Reese TS (1969) Junctions between intimately apposed cell membranes in the vertebrate brain. J Cell Biol 3:648–677

    Article  Google Scholar 

  3. Goldmann EE (1913) VitalFarbung am Zentralnervensystem. Abh Preuss Akad Wissensch PhysMath K1:1–60

    Google Scholar 

  4. Zlokovic BV (2008) The blood–brain barrier in health and chronic neurodegenerative disorders. Neuron 2:178–201

    Article  CAS  Google Scholar 

  5. Paris L, Tonutti L, Vannini C, Bazzoni G (2008) Structural organization of the tight junctions. Biochim Biophys Acta 3:646–659

    Google Scholar 

  6. Bundgaard M, Abbott NJ (2008) All vertebrates started out with a glial blood–brain barrier 4–500 million years ago. Glia 7:699–708

    Article  Google Scholar 

  7. Lee SW, Kim WJ, Choi YK, Song HS, Son MJ, Gelman IH, Kim YJ, Kim KW (2003) SSeCKS regulates angiogenesis and tight junction formation in blood–brain barrier. Nat Med 7:900–906

    Article  CAS  Google Scholar 

  8. Wosik K, Cayrol R, Dodelet-Devillers A, Berthelet F, Bernard M, Moumdjian R, Bouthillier A, Reudelhuber TL, Prat A (2007) Angiotensin II controls occludin function and is required for blood brain barrier maintenance: relevance to multiple sclerosis. J Neurosci 34:9032–9042

    Article  CAS  Google Scholar 

  9. Prat A, Biernacki K, Wosik K, Antel JP (2001) Glial cell influence on the human blood–brain barrier. Glia 2:145–155

    Article  Google Scholar 

  10. Pachter JS, de Vries HE, Fabry Z (2003) The blood–brain barrier and its role in immune privilege in the central nervous system. J Neuropathol Exp Neurol 6:593–604

    Google Scholar 

  11. van Horssen J, Brink BP, de Vries HE, van der Valk P, Be L (2007) The blood–brain barrier in cortical multiple sclerosis lesions. J Neuropathol Exp Neurol 4:321–328

    Article  Google Scholar 

  12. Garberg P, Ball M, Borg N, Cecchelli R, Fenart L, Hurst RD, Lindmark T, Mabondzo A, Nilsson JE, Raub TJ, Stanimirovic D, Terasaki T, Oberg JO, Osterberg T (2005) In vitro models for the blood–brain barrier. Toxicol In Vitro 3:299–334

    Article  CAS  Google Scholar 

  13. Armulik A, Abramsson A, Betsholtz C (2005) Endothelial/pericyte interactions. Circ Res 6:512–523

    Article  CAS  Google Scholar 

  14. Jacobson K, Mouritsen OG, Anderson RG (2007) Lipid rafts: at a crossroad between cell biology and physics. Nat Cell Biol 1:7–14

    Article  CAS  Google Scholar 

  15. Viola A, Gupta N (2007) Tether and trap: regulation of membrane-raft dynamics by actin-binding proteins. Nat Rev Immunol 11:889–896

    Article  CAS  Google Scholar 

  16. Mishra S, Joshi PG (2007) Lipid raft heterogeneity: an enigma. J Neurochem 103:135–142

    Article  PubMed  CAS  Google Scholar 

  17. Foster LJ, Chan QW (2007) Lipid raft proteomics: more than just detergent-resistant membranes. Subcell Biochem 43:35–47

    Article  PubMed  Google Scholar 

  18. Munro S (2003) Lipid rafts: elusive or illusive? Cell 4:377–388

    Article  Google Scholar 

  19. Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 6633:569–572

    Article  CAS  Google Scholar 

  20. Manes S, Viola A (2006) Lipid rafts in lymphocyte activation and migration. Mol Membr Biol 1:59–69

    Article  CAS  Google Scholar 

  21. Becher A, McIlhinney RA (2005) Consequences of lipid raft association on G-protein-coupled receptor function. Biochem Soc Symp 72:151–164

    PubMed  CAS  Google Scholar 

  22. Gomez-Mouton C, Abad JL, Mira E, Lacalle RA, Gallardo E, Jimenez-Baranda S, Illa I, Bernad A, Manes S, Martinez A (2001) Segregation of leading-edge and uropod components into specific lipid rafts during T cell polarization. Proc Natl Acad Sci U S A 17:9642–9647

    Article  Google Scholar 

  23. Manes S, Mira E, Gomez-Mouton C, Lacalle RA, Keller P, Labrador JP, Martinez A (1999) Membrane raft microdomains mediate front-rear polarity in migrating cells. EMBO J 22:6211–6220

    Article  Google Scholar 

  24. Shaw AS (2006) Lipid rafts: now you see them, now you don’t. Nat Immunol 11:1139–1142

    Article  CAS  Google Scholar 

  25. Chamberlain LH (2004) Detergents as tools for the purification and classification of lipid rafts. FEBS Lett 1–3:1–5

    Article  CAS  Google Scholar 

  26. Chen X, Morris R, Lawrence MJ, Quinn PJ (2007) The isolation and structure of membrane lipid rafts from rat brain. Biochimie 2:192–196

    Article  CAS  Google Scholar 

  27. Delaunay JL, Breton M, Trugnan G, Maurice M (2008) Differential solubilization of inner plasma membrane leaflet components by Lubrol WX and Triton X-100. Biochim Biophys Acta 1:105–112

    Google Scholar 

  28. Gil C, Cubi R, Blasi J, Aguilera J (2006) Synaptic proteins associate with a sub-set of lipid rafts when isolated from nerve endings at physiological temperature. Biochem Biophys Res Commun 4:1334–1342

    Article  CAS  Google Scholar 

  29. Pike LJ, Han X, Chung KN, Gross RW (2002) Lipid rafts are enriched in arachidonic acid and plasmenylethanolamine and their composition is independent of caveolin-1 expression: a quantitative electrospray ionization/mass spectrometric analysis. Biochemistry 6:2075–2088

    Article  CAS  Google Scholar 

  30. McCaffrey G, Seelbach MJ, Staatz WD, Nametz N, Quigley C, Campos CR, Brooks TA, Davis TP (2008) Occludin oligomeric assembly at tight junctions of the blood–brain barrier is disrupted by peripheral inflammatory hyperalgesia. J Neurochem 106:2395–2409

    Article  PubMed  CAS  Google Scholar 

  31. McCaffrey G, Staatz WD, Quigley CA, Nametz N, Seelbach MJ, Campos CR, Brooks TA, Egleton RD, Davis TP (2007) Tight junctions contain oligomeric protein assembly critical for maintaining blood–brain barrier integrity in vivo. J Neurochem 103:2540–2555

    Article  CAS  Google Scholar 

  32. Schuck S, Simons K (2004) Polarized sorting in epithelial cells: raft clustering and the biogenesis of the apical membrane. J Cell Sci Pt 25:5955–5964

    Article  CAS  Google Scholar 

  33. Nguyen DH, Giri B, Collins G, Taub DD (2005) Dynamic reorganization of chemokine receptors, cholesterol, lipid rafts, and adhesion molecules to sites of CD4 engagement. Exp Cell Res 2:559–569

    Article  CAS  Google Scholar 

  34. Gomez-Mouton C, Lacalle RA, Mira E, Jimenez-Baranda S, Barber DF, Carrera AC, Martinez A, Manes S (2004) Dynamic redistribution of raft domains as an organizing platform for signaling during cell chemotaxis. J Cell Biol 5:759–768

    Article  CAS  Google Scholar 

  35. Mestas J, Hughes CC (2001) Endothelial cell costimulation of T cell activation through CD58-CD2 interactions involves lipid raft aggregation. J Immunol 8:4378–4385

    Google Scholar 

  36. Song L, Ge S, Pachter JS (2006) Caveolin-1 regulates expression of junction-associated proteins in brain microvascular endothelial cells. Blood 109:1515–1523

    Article  PubMed  CAS  Google Scholar 

  37. Pohl J, Ring A, Ehehalt R, Schulze-Bergkamen H, Schad A, Verkade P, Stremmel W (2004) Long-chain fatty acid uptake into adipocytes depends on lipid raft function. Biochemistry 14:4179–4187

    Article  CAS  Google Scholar 

  38. Sprenger RR, Fontijn RD, van Marle J, Pannekoek H, Horrevoets AJ (2006) Spatial segregation of transport and signalling functions between human endothelial caveolae and lipid raft proteomes. Biochem J 3:401–410

    Google Scholar 

  39. Tang VW (2006) Proteomic and bioinformatic analysis of epithelial tight junction reveals an unexpected cluster of synaptic molecules. Biol Direct 1:37

    Article  PubMed  CAS  Google Scholar 

  40. Barreiro O, Zamai M, Yanez-Mo M, Tejera E, Lopez-Romero P, Monk PN, Gratton E, Caiolfa VR, Sanchez-Madrid F (2008) Endothelial adhesion receptors are recruited to adherent leukocytes by inclusion in preformed tetraspanin nanoplatforms. J Cell Biol 3:527–542

    Article  CAS  Google Scholar 

  41. Levy S, Shoham T (2005) Protein–protein interactions in the tetraspanin web. Physiology 20:218–224

    Article  PubMed  CAS  Google Scholar 

  42. Levy S, Shoham T (2005) The tetraspanin web modulates immune-signalling complexes. Nat Rev Immunol 2:136–148

    Article  CAS  Google Scholar 

  43. Barreiro O, de la Fuente H, Mittelbrunn M, Sanchez-Madrid F (2007) Functional insights on the polarized redistribution of leukocyte integrins and their ligands during leukocyte migration and immune interactions. Immunol Rev 218:147–164

    Article  PubMed  CAS  Google Scholar 

  44. Forster C (2008) Tight junctions and the modulation of barrier function in disease. Histochem Cell Biol 1:55–70

    Article  CAS  Google Scholar 

  45. Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD (2006) Blood–brain barrier: structural components and function under physiologic and pathologic conditions. J Neuroimmune Pharmacol 3:223–236

    Article  Google Scholar 

  46. Leech S, Kirk J, Plumb J, McQuaid S (2007) Persistent endothelial abnormalities and blood–brain barrier leak in primary and secondary progressive multiple sclerosis. Neuropathol Appl Neurobiol 1:86–98

    Google Scholar 

  47. Allen IV, McQuaid S, Mirakhur M, Nevin G (2001) Pathological abnormalities in the normal-appearing white matter in multiple sclerosis. Neurol Sci 2:141–144

    Article  Google Scholar 

  48. Yang Y, Estrada EY, Thompson JF, Liu W, Rosenberg GA (2007) Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat. J Cereb Blood Flow Metab 4:697–709

    Google Scholar 

  49. Pokutta S, Drees F, Yamada S, Nelson WJ, Weis WI (2008) Biochemical and structural analysis of alpha-catenin in cell–cell contacts. Biochem Soc Trans Pt 2:141–147

    Article  CAS  Google Scholar 

  50. Weber C, Fraemohs L, Dejana E (2007) The role of junctional adhesion molecules in vascular inflammation. Nat Rev Immunol 6:467–477

    Article  CAS  Google Scholar 

  51. Nelson WJ (2008) Regulation of cell–cell adhesion by the cadherin–catenin complex. Biochem Soc Trans Pt 2:149–155

    Article  CAS  Google Scholar 

  52. Nyqvist D, Giampietro C, Dejana E (2008) Deciphering the functional role of endothelial junctions by using in vivo models. EMBO Rep 8:742–747

    Article  CAS  Google Scholar 

  53. Dejana E, Orsenigo F, Lampugnani MG (2008) The role of adherens junctions and VE-cadherin in the control of vascular permeability. J Cell Sci Pt 13:2115–2122

    Article  CAS  Google Scholar 

  54. Danese S, Dejana E, Fiocchi C (2007) Immune regulation by microvascular endothelial cells: directing innate and adaptive immunity, coagulation, and inflammation. J Immunol 10:6017–6022

    Google Scholar 

  55. del Zoppo GJ, Milner R, Mabuchi T, Hung S, Wang X, Koziol JA (2006) Vascular matrix adhesion and the blood–brain barrier. Biochem Soc Trans Pt 6:1261–1266

    Google Scholar 

  56. Del Pozo MA (2004) Integrin signaling and lipid rafts. Cell Cycle 6:725–728

    Google Scholar 

  57. Nusrat A, Parkos CA, Verkade P, Foley CS, Liang TW, Innis-Whitehouse W, Eastburn KK, Madara JL (2000) Tight junctions are membrane microdomains. J Cell Sci 113:1771–1781

    PubMed  CAS  Google Scholar 

  58. Turowski P, Martinelli R, Crawford R, Wateridge D, Papageorgiou AP, Lampugnani MG, Gamp AC, Vestweber D, Adamson P, Dejana E, Greenwood J (2008) Phosphorylation of vascular endothelial cadherin controls lymphocyte emigration. J Cell Sci Pt 1:29–37

    Article  CAS  Google Scholar 

  59. Itoh M, Nagafuchi A, Yonemura S, Kitani-Yasuda T, Tsukita S, Tsukita S (1993) The 220-kD protein colocalizing with cadherins in non-epithelial cells is identical to ZO-1, a tight junction-associated protein in epithelial cells: cDNA cloning and immunoelectron microscopy. J Cell Biol 3:491–502

    Article  Google Scholar 

  60. Van Itallie CM, Gambling TM, Carson JL, Anderson JM (2005) Palmitoylation of claudins is required for efficient tight-junction localization. J Cell Sci Pt 7:1427–1436

    Article  CAS  Google Scholar 

  61. Nag S, Venugopalan R, Stewart DJ (2007) Increased caveolin-1 expression precedes decreased expression of occludin and claudin-5 during blood-brain barrier breakdown. Acta Neuropathol 5:459–469

    Article  CAS  Google Scholar 

  62. Schubert W, Frank PG, Razani B, Park DS, Chow CW, Lisanti MP (2001) Caveolae-deficient endothelial cells show defects in the uptake and transport of albumin in vivo. J Biol Chem 52:48619–48622

    Article  CAS  Google Scholar 

  63. Lee DB, Jamgotchian N, Allen SG, Abeles MB, Ward HJ (2008) A lipid–protein hybrid model for tight junction. Am J Physiol Renal Physiol 6:F1601–F1612

    Article  CAS  Google Scholar 

  64. Lynch RD, Francis SA, McCarthy KM, Casas E, Thiele C, Schneeberger EE (2007) Cholesterol depletion alters detergent-specific solubility profiles of selected tight junction proteins and the phosphorylation of occludin. Exp Cell Res 12:2597–2610

    Article  CAS  Google Scholar 

  65. Lambert D, O’Neill CA, Padfield PJ (2007) Methyl-beta-cyclodextrin increases permeability of Caco-2 cell monolayers by displacing specific claudins from cholesterol rich domains associated with tight junctions. Cell Physiol Biochem 5:495–506

    Article  CAS  Google Scholar 

  66. Ifergan I, Wosik K, Cayrol R, Kebir H, Auger C, Bernard M, Bouthillier A, Moumdjian R, Duquette P, Prat A (2006) Statins reduce human blood–brain barrier permeability and restrict leukocyte migration: relevance to multiple sclerosis. Ann Neurol 1:45–55

    Article  CAS  Google Scholar 

  67. Greenwood J, Mason JC (2007) Statins and the vascular endothelial inflammatory response. Trends Immunol 2:88–98

    Article  CAS  Google Scholar 

  68. Dimitrijevic OB, Stamatovic SM, Keep RF, Andjelkovic AV (2006) Effects of the chemokine CCL2 on blood–brain barrier permeability during ischemia–reperfusion injury. J Cereb Blood Flow Metab 6:797–810

    Article  CAS  Google Scholar 

  69. Song L, Pachter JS (2004) Monocyte chemoattractant protein-1 alters expression of tight junction-associated proteins in brain microvascular endothelial cells. Microvasc Res 1:78–89

    Article  CAS  Google Scholar 

  70. van Horssen J, Bo L, Dijkstra CD, de Vries HE (2006) Extensive extracellular matrix depositions in active multiple sclerosis lesions. Neurobiol Dis 3:484–491

    Google Scholar 

  71. Sixt M, Engelhardt B, Pausch F, Hallmann R, Wendler O, Sorokin LM (2001) Endothelial cell laminin isoforms, laminins 8 and 10, play decisive roles in T cell recruitment across the blood-brain barrier in experimental autoimmune encephalomyelitis. J Cell Biol 5:933–946

    Article  Google Scholar 

  72. Wary KK, Mariotti A, Zurzolo C, Giancotti FG (1998) A requirement for caveolin-1 and associated kinase Fyn in integrin signaling and anchorage-dependent cell growth. Cell 5:625–634

    Article  Google Scholar 

  73. Carman CV, Springer TA (2008) Trans-cellular migration: cell–cell contacts get intimate. Curr Opin Cell Biol 20:533–540

    Article  PubMed  CAS  Google Scholar 

  74. Carman CV, Springer TA (2004) A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them. J Cell Biol 2:377–388

    Article  Google Scholar 

  75. Engelhardt B, Kempe B, Merfeld-Clauss S, Laschinger M, Furie B, Wild MK, Vestweber D (2005) P-selectin glycoprotein ligand 1 is not required for the development of experimental autoimmune encephalomyelitis in SJL and C57BL/6 mice. J Immunol 2:1267–1275

    Google Scholar 

  76. Kiely JM, Hu Y, Garcia-Cardena G, Gimbrone MA Jr (2003) Lipid raft localization of cell surface E-selectin is required for ligation-induced activation of phospholipase C gamma. J Immunol 6:3216–3224

    Google Scholar 

  77. Kerfoot SM, Kubes P (2002) Overlapping roles of P-selectin and alpha 4 integrin to recruit leukocytes to the central nervous system in experimental autoimmune encephalomyelitis. J Immunol 2:1000–1006

    Google Scholar 

  78. Kerfoot SM, Norman MU, Lapointe BM, Bonder CS, Zbytnuik L, Kubes P (2006) Reevaluation of P-selectin and alpha 4 integrin as targets for the treatment of experimental autoimmune encephalomyelitis. J Immunol 10:6225–6234

    Google Scholar 

  79. Doring A, Wild M, Vestweber D, Deutsch U, Engelhardt B (2007) E- and P-selectin are not required for the development of experimental autoimmune encephalomyelitis in C57BL/6 and SJL mice. J Immunol 12:8470–8479

    Google Scholar 

  80. Uboldi C, Doring A, Alt C, Estess P, Siegelman M, Engelhardt B (2008) L-Selectin-deficient SJL and C57BL/6 mice are not resistant to experimental autoimmune encephalomyelitis. Eur J Immunol 8:2156–2167

    Article  CAS  Google Scholar 

  81. Piccio L, Rossi B, Scarpini E, Laudanna C, Giagulli C, Issekutz AC, Vestweber D, Butcher EC, Constantin G (2002) Molecular mechanisms involved in lymphocyte recruitment in inflamed brain microvessels: critical roles for P-selectin glycoprotein ligand-1 and heterotrimeric G(i)-linked receptors. J Immunol 4:1940–1949

    Google Scholar 

  82. Reiss Y, Hoch G, Deutsch U, Engelhardt B (1998) T cell interaction with ICAM-1-deficient endothelium in vitro: essential role for ICAM-1 and ICAM-2 in transendothelial migration of T cells. Eur J Immunol 10:3086–3099

    Article  Google Scholar 

  83. Lyck R, Reiss Y, Gerwin N, Greenwood J, Adamson P, Engelhardt B (2003) T-cell interaction with ICAM-1/ICAM-2 double-deficient brain endothelium in vitro: the cytoplasmic tail of endothelial ICAM-1 is necessary for transendothelial migration of T cells. Blood 10:3675–3683

    Article  CAS  Google Scholar 

  84. Floris S, Ruuls SR, Wierinckx A, van der Pol SM, Dopp E, van der Meide PH, Dijkstra CD, de Vries HE (2002) Interferon-beta directly influences monocyte infiltration into the central nervous system. J Neuroimmunol 1–2:69–79

    Article  Google Scholar 

  85. Seguin R, Biernacki K, Rotondo RL, Prat A, Antel JP (2003) Regulation and functional effects of monocyte migration across human brain-derived endothelial cells. J Neuropathol Exp Neurol 4:412–419

    Google Scholar 

  86. Ifergan I, Kebir H, Bernard M, Wosik K, Dodelet-Devillers A, Cayrol R, Arbour N, Prat A (2008) The blood–brain barrier induces differentiation of migrating monocytes into Th17-polarizing dendritic cells. Brain Pt 3:785–799

    Article  Google Scholar 

  87. Muller WA (2001) Migration of leukocytes across endothelial junctions: some concepts and controversies. Microcirculation 3:181–193

    Article  CAS  Google Scholar 

  88. Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 2:301–314

    Article  Google Scholar 

  89. Ley K, Laudanna C, Cybulsky MI, Nourshargh S (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 9:678–689

    Article  CAS  Google Scholar 

  90. Graesser D, Solowiej A, Bruckner M, Osterweil E, Juedes A, Davis S, Ruddle NH, Engelhardt B, Madri JA (2002) Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1-deficient mice. J Clin Invest 3:383–392

    Google Scholar 

  91. Amos C, Romero IA, Schultze C, Rousell J, Pearson JD, Greenwood J, Adamson P (2001) Cross-linking of brain endothelial intercellular adhesion molecule (ICAM)-1 induces association of ICAM-1 with detergent-insoluble cytoskeletal fraction. Arterioscler Thromb Vasc Biol 5:810–816

    Google Scholar 

  92. Muller WA, Weigl SA, Deng X, Phillips DM (1993) PECAM-1 is required for transendothelial migration of leukocytes. J Exp Med 2:449–460

    Article  Google Scholar 

  93. Millan J, Hewlett L, Glyn M, Toomre D, Clark P, Ridley AJ (2006) Lymphocyte transcellular migration occurs through recruitment of endothelial ICAM-1 to caveola- and F-actin-rich domains. Nat Cell Biol 2:113–123

    Article  CAS  Google Scholar 

  94. Mills JH, Thompson LF, Mueller C, Waickman AT, Jalkanen S, Niemela J, Airas L, Bynoe MS (2008) CD73 is required for efficient entry of lymphocytes into the central nervous system during experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 27:9325–9330

    Article  Google Scholar 

  95. Wetzel A, Chavakis T, Preissner KT, Sticherling M, Haustein UF, Anderegg U, Saalbach A (2004) Human Thy-1 (CD90) on activated endothelial cells is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J Immunol 6:3850–3859

    Google Scholar 

  96. Drenkard D, Becke FM, Langstein J, Spruss T, Kunz-Schughart LA, Tan TE, Lim YC, Schwarz H (2007) CD137 is expressed on blood vessel walls at sites of inflammation and enhances monocyte migratory activity. FASEB J 2:456–463

    Article  CAS  Google Scholar 

  97. Dijkstra S, Kooij G, Verbeek R, van der Pol SM, Amor S, Geisert EE Jr, Dijkstra CD, van Noort JM, Vries HE (2008) Targeting the tetraspanin CD81 blocks monocyte transmigration and ameliorates EAE. Neurobiol Dis 3:413–421

    Article  CAS  Google Scholar 

  98. Bixel G, Kloep S, Butz S, Petri B, Engelhardt B, Vestweber D (2004) Mouse CD99 participates in T-cell recruitment into inflamed skin. Blood 10:3205–3213

    Article  CAS  Google Scholar 

  99. Cayrol R, Wosik K, Berard JL, Dodelet-Devillers A, Ifergan I, Kebir H, Haqqani AS, Kreymborg K, Krug S, Moumdjian R, Bouthillier A, Becher B, Arbour N, David S, Stanimirovic D, Prat A (2008) Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system. Nat Immunol 2:137–145

    Article  CAS  Google Scholar 

  100. Carman CV, Jun CD, Salas A, Springer TA (2003) Endothelial cells proactively form microvilli-like membrane projections upon intercellular adhesion molecule 1 engagement of leukocyte LFA-1. J Immunol 11:6135–6144

    Google Scholar 

  101. Barreiro O, Yanez-Mo M, Sala-Valdes M, Gutierrez-Lopez MD, Ovalle S, Higginbottom A, Monk PN, Cabanas C, Sanchez-Madrid F (2005) Endothelial tetraspanin microdomains regulate leukocyte firm adhesion during extravasation. Blood 7:2852–2861

    Article  CAS  Google Scholar 

  102. Barreiro O, Vicente-Manzanares M, Urzainqui A, Yanez-Mo M, Sanchez-Madrid F (2004) Interactive protrusive structures during leukocyte adhesion and transendothelial migration. Front Biosci 9:1849–1863

    Article  PubMed  CAS  Google Scholar 

  103. Barreiro O, Yanez-Mo M, Serrador JM, Montoya MC, Vicente-Manzanares M, Tejedor R, Furthmayr H, Sanchez-Madrid F (2002) Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes. J Cell Biol 7:1233–1245

    Article  Google Scholar 

  104. Ridley AJ (2001) Rho proteins: linking signaling with membrane trafficking. Traffic 5:303–310

    Article  Google Scholar 

  105. Honing H, Van Den Berg TK, van der Pol SM, Dijkstra CD, van der Kammen RA, Collard JG, de Vries HE (2004) RhoA activation promotes transendothelial migration of monocytes via ROCK. J Leukoc Biol 3:523–528

    Google Scholar 

  106. Stamatovic SM, Keep RF, Kunkel SL, Andjelkovic AV (2003) Potential role of MCP-1 in endothelial cell tight junction ‘opening’: signaling via Rho and Rho kinase. J Cell Sci Pt 22:4615–4628

    Article  CAS  Google Scholar 

  107. Prieto-Sanchez RM, Berenjeno IM, Bustelo XR (2006) Involvement of the Rho/Rac family member RhoG in caveolar endocytosis. Oncogene 21:2961–2973

    Article  CAS  Google Scholar 

  108. Fujitani M, Honda A, Hata K, Yamagishi S, Tohyama M, Yamashita T (2005) Biological activity of neurotrophins is dependent on recruitment of Rac1 to lipid rafts. Biochem Biophys Res Commun 1:150–154

    Article  CAS  Google Scholar 

  109. Ishmael JE, Safic M, Amparan D, Vogel WK, Pham T, Marley K, Filtz TM, Maier CS (2007) Nonmuscle myosins II-B and Va are components of detergent-resistant membrane skeletons derived from mouse forebrain. Brain Res 1143:46–59

    Article  PubMed  CAS  Google Scholar 

  110. Li Q, Zhang Q, Zhang M, Wang C, Zhu Z, Li N, Li J (2008) Effect of n-3 polyunsaturated fatty acids on membrane microdomain localization of tight junction proteins in experimental colitis. FEBS J 3:411–420

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Neuroimmunology Research Laboratory, Center of Excellence in Neuromics, CHUM-Notre-Dame Hospital, Faculty of Medicine, Université de Montréal, Montréal, Quebec, Canada

    Aurore Dodelet-Devillers, Romain Cayrol & Alexandre Prat

  2. Department of Molecular Cell Biology and Immunology, VU Medical Center, Amsterdam, the Netherlands

    Jack van Horssen & Helga E. de Vries

  3. Institute for Biological Sciences, National Research Council, Ottawa, Ontario, Canada

    Arsalan S. Haqqani

  4. Theodor Kocher Institute, University of Bern, Bern, Switzerland

    Britta Engelhardt

  5. Department of Cell Biology, Institute of Ophthalmology, University College London, London, UK

    John Greenwood

  6. Multiple Sclerosis Clinic, Department of Neurology, Faculty of Medicine, Université de Montréal, CHUM-Notre-Dame Hospital, Montréal, Quebec, Canada

    Alexandre Prat

  7. Center of Excellence in Neuromics, Neuroimmunology Research Laboratory, Y-3608, CHUM-Hopital Notre-Dame, 1560 Sherbrooke East, Montreal, Quebec, Canada, H2L 4M1

    Alexandre Prat

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  1. Aurore Dodelet-Devillers
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  2. Romain Cayrol
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  4. Arsalan S. Haqqani
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  5. Helga E. de Vries
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Dodelet-Devillers, A., Cayrol, R., van Horssen, J. et al. Functions of lipid raft membrane microdomains at the blood–brain barrier. J Mol Med 87, 765–774 (2009). https://doi.org/10.1007/s00109-009-0488-6

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  • DOI: https://doi.org/10.1007/s00109-009-0488-6

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