Cellular and Molecular Neurobiology

, Volume 20, Issue 1, pp 57–76 | Cite as

Tight Junctions of the Blood–Brain Barrier

  • Uwe Kniesel
  • Hartwig Wolburg
Article

Abstract

1. The blood–brain barrier is essential for the maintainance and regulation of the neural microenvironment. The blood–brain barrier endothelial cells comprise an extremely low rate of transcytotic vesicles and a restrictive paracellular diffusion barrier. The latter is realized by the tight junctions between the endothelial cells of the brain microvasculature, which are subject of this review. Morphologically, blood–brain barrier-tight junctions are more similar to epithelial tight junctions than to endothelial tight junctions in peripheral blood vessels.

2. Although blood–brain barrier-tight junctions share many characteristics with epithelial tight junctions, there are also essential differences. However, in contrast to tight junctions in epithelial systems, structural and functional characteristics of tight junctions in endothelial cells are highly sensitive to ambient factors.

3. Many ubiquitous molecular constituents of tight junctions have been identified and characterized including claudins, occludin, ZO-1, ZO-2, ZO-3, cingulin, and 7H6. Signaling pathways involved in tight junction regulation comprise, among others, G-proteins, serine, threonine, and tyrosine kinases, extra- and intracellular calcium levels, cAMP levels, proteases, and TNFα. Common to most of these pathways is the modulation of cytoskeletal elements which may define blood–brain barrier characteristics. Additionally, cross-talk between components of the tight junction– and the cadherin–catenin system suggests a close functional interdependence of the two cell–cell contact systems.

4. Recent studies were able to elucidate crucial aspects of the molecular basis of tight junction regulation. An integration of new results into previous morphological work is the central intention of this review.

tight junction blood–brain barrier morphology freeze–fracture cadherins catenins occludin cytoskeleton 

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REFERENCES

  1. Aaku-Saraste, E., Hellwig, A., and Huttner, W. B. (1996). Loss of occludin and functional tight junctions, but not ZO-1, during neural tube closure-Remodeling of the neuroepithelium prior to neurogenesis. Dev. Biol. 180:664–679.PubMedGoogle Scholar
  2. Abbott, N. J., Hughes, C. C. W., Revest, P. A., and Greenwood, J. (1992). Development and characterization of a rat capillary endothelial culture. Towards an in vitro BBB. J. Cell Sci. 103:23–38.PubMedGoogle Scholar
  3. Anderson, J. M. (1997). MAGUK magic. Curr. Biol. 6:382–384.Google Scholar
  4. Anderson, J. M., and Van Itallie, C. M. (1995). Tight junctions and the molecular basis for regulation of paracellular permeability. Am. J. Physiol. 269:G467-G475.PubMedGoogle Scholar
  5. Ando-Akatsuka, Y., Saitou, M., Hirase, T., Kishi, M., Sakaqkibara, A., Itoh, M., Yonemura, S., Furuse, M., and Tsukita, S. (1996). Interspecies diversity of the occludin sequence: cDNA cloning of human, mouse, dog, and rat-kangaroo homologues. J. Cell Biol. 133:43–48.PubMedGoogle Scholar
  6. Arthur, F. E., Shivers, R. R., and Bowman, P. D. (1987). Astrocyte-mediated induction of tight junctions in brain capillary endothelium: An efficient in vitro model. Dev. Brain Res. 36:155–159.Google Scholar
  7. Bacallao, R., Garfinkel, A., Monke, S., Zampighi, G., and Mandel, L. J. (1994). ATP-depletion: A novel method to study junctional properties in epithelial tissues. I. Rearrangement of the actin cytoskeleton. J. Cell Sci. 107:3301–3313.PubMedGoogle Scholar
  8. Balda, M. S., and Anderson, J. M. (1993). Two classes of tight junctions are revealed by ZO-1 isoforms. Am. J. Physiol. 264:C918-C924.PubMedGoogle Scholar
  9. Balda, M. S., and Matter, K. (1998). Tight junctions. J. Cell Sci. 111:541–547.PubMedGoogle Scholar
  10. Balda, M. S., Gonzales-Mariscal, L., Contreras, R. G., Macias-Silva, M., Torres-Marques, M. E., Garcia-Sainz, J. A., and Cereijido, M. (1991). Assembly and sealing of tight junctions: possible participation of G-proteins, phospholipase C, protein kinase C and calmodulin. J. Membr. Biol. 122:193–202.PubMedGoogle Scholar
  11. Balda, M. S., Gonzales-Mariscal, L., Matter, K., Cereijido, M., and Anderson, J. M. (1993). Assembly of tight junction. The role of diacylglycerol. J. Cell Biol. 123:293–302.PubMedGoogle Scholar
  12. Balda, M. S., Whitney, J. A., Flores, C., Gonzáles, S., Cereijido, M., and Matter, K. (1996). Functional dissociation of paracellular permeability and transepithelial electrical resistance and disruption of the apical-basolateral intramembrane diffusion barrier by expression of a mutant tight junction membrane protein. J. Cell Biol. 134:1031–1049.PubMedGoogle Scholar
  13. Bauer, H. C., Bauer, H., Lamet-Schwandtner, A., Amberger, A., Ruiz, P., and Steiner, M. (1993). Neovascularization and the appearance of morphological characteristics of the blood-brain barrier in the embryonic mouse central nervous system. Dev. Brain Res. 75:269–278.Google Scholar
  14. Bentzel, C. J., Hainau, B., Ho, S., Hui, S. W., Edelman, A., Anagnostopoulos, T., and Benedetti, E. L. (1980). Cytoplasmic regulation of tight junction permeability: Effect of plant cytokinins. Am. J. Physiol. 239:C75-C89.PubMedGoogle Scholar
  15. Brightman, M. W., and Reese, T. S. (1969). Junctions between intimately apposed cell membranes in the vertebrate brain. J. Cell Biol. 40:648–677.PubMedGoogle Scholar
  16. Bundgaard, M., and Cserr, H. F. (1981). A glial blood-brain barrier in elasmobranchs. Brain Res. 226:61–74.PubMedGoogle Scholar
  17. Butt, A. M., Jones, H. C., and Abbott, N. J. (1990). Electrical resistance across the blood-brain barrier in anaesthetized rats: A developmental study. J. Physiol. 429:47–62.PubMedGoogle Scholar
  18. Cassella, J. P., Lawrenson, J. G., and Firth, J. A. (1997). Development of endothelial paracellular clefts and their tight junctions in the pial microvessels of the rat. J. Neurocytol. 26:567–575.PubMedGoogle Scholar
  19. Chen, Y., Merzdorf, C., Paul., D. L., and Goodenough, D. A. (1997). COOH terminus of occludin is required for tight junction barrier function in early Xenopus embryos. J. Cell Biol. 138:891–899.PubMedGoogle Scholar
  20. Citi, S. (1992). Protein kinase inhibitors prevent junction dissociation induced by low extracellular calcium in MDCK epithelial cells. J. Cell Biol. 117:169–178.PubMedGoogle Scholar
  21. Citi, S., and Denisenko, N. (1995). Phosphorylation of the tight junction protein cingulin and the effects of protein kinase inhibitors and activators in MDCK epithelial cells. J. Cell Sci. 108:2917–2926.PubMedGoogle Scholar
  22. Citi, S., Sabanay, H., Kendrick-Jones, J., and Geiger, B. (1989). Cingulin: Characterization and localization. J. Cell Sci. 93:107–122.PubMedGoogle Scholar
  23. Claude, P. (1978). Morphologic factors influencing transepithelial permeability. A model for the resistance of the zonula occludens. J. Membr. Biol. 39:219–232.PubMedGoogle Scholar
  24. Claude, P., and Goodenough, D. A. (1973). Fracture faces of zonulae occludentes from “tight” and “leaky” epithelia. J. Cell Biol. 58:390–400.PubMedGoogle Scholar
  25. Contreras, R. G., Miller, J. H., Zamora, M., Gonzales-Mariscal, L., and Cereijido, M. (1992). Interaction of calcium with plasma membrane of epithelial (MDCK) cells during junction formation. Am. J. Physiol. 263:C313-C318.PubMedGoogle Scholar
  26. Coomber, B. L., Stewart, P. A., Hayakawa, K., Farrell, C. L., and DelMaestro, R. F. (1987). Quantitative morphology of human glioblastoma multifome microvessels: Structural basis of blood-brain barrier defect. J. Neuro-Oncol. 5:299–307.Google Scholar
  27. D'Angelo Siliciano, J., and Goodenough, D. A. (1988). Localization of the tight junction protein, ZO-1, is modulated by extracellular calcium ion. J. Cell Biol. 107:2389–2399.PubMedGoogle Scholar
  28. Dehouck, B., Dehouck, M.-P., Fruchart, J.-C., and Cecchelli, R. (1994). Upregulation of the low density lipoprotein receptor at the blood-brain barrier: Intercommunications between brain capillary ECs and astrocytes. J. Cell Biol. 126:465–474.PubMedGoogle Scholar
  29. Denisenko, N., Burighel, P., and Citi, S. (1994). Different effects of protein kinase inhibitors on the localization of junctional proteins at cell-cell contact sites. J. Cell Sci. 107:969–981.PubMedGoogle Scholar
  30. Denker, B. M., and Nigam, S. K. (1998) Molecular structure and assembly of the tight junction. Am. J. Physiol. 274:F1-F9.PubMedGoogle Scholar
  31. Fabian, R. H., and Hulsebosch, C. E. (1989). Time course of penetration of xenogenic IgG into the central nervous system of the neonatal rat: An immunohistochemical and radionuclide tracer study. J. Neuroimmunol. 24:183–189.PubMedGoogle Scholar
  32. Fallier-Becker, P., Betz, E., Wolburg-Buchholz, K., and Fotev, Z. (1991). Fibromuscular proliferates induced in vitro using a trans-filter culture system. Res. Exp. Med. 191:11–25.Google Scholar
  33. Farquhar, M. G., and Palade, G. E. (1963). Junctional complexes in various epithelia. J. Cell Biol. 17:375–412.PubMedGoogle Scholar
  34. Folkman, J. (1995). Clinical applications of research on angiogenesis. N. Engl. J. Med. 333:1757–1763.CrossRefPubMedGoogle Scholar
  35. Fujimoto, K. (1995). Freeze-fracture replica electron microscopy combined with SDS digestion for cytochemical labeling of integral membrane proteins. Application to the immunogold labeling of intercellular junctional complexes. J. Cell Sci. 108:3443–3449.PubMedGoogle Scholar
  36. Furuse, M., Hirase, T., Itoh, M., Nagafuchi, A., Yonemura, S., and Tsukita, S. (1993). Occludin: A novel integral membrane protein localizing at tight junctions. J. Cell Biol. 123:1777–1788.CrossRefPubMedGoogle Scholar
  37. Furuse, M., Itoh, M., Hirase, T., Nagafuchi, A., Yonemura, S., and Tsukita, S. (1994). Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions. J. Cell Biol. 127:1617–1626.PubMedGoogle Scholar
  38. Furuse, M., Fujimoto, K., Sato, N., Hirase, T., and Tsukita, S. (1996). Overexpression of occludin, a tight junction-associated integral membrane protein, induces the formation of intracellular multilamellar bodies bearing tight junction-like structures. J. Cell Sci. 109:429–435.PubMedGoogle Scholar
  39. Furuse, M., Fujita, K., Hiiragi, T., Fujimoto, K., and Tsukita, S. (1998). Claudin-1 and-2: Novel integral membrane proteins localizing at tight junctions. J. Cell Biol. 141:1539–1550.PubMedGoogle Scholar
  40. Gerhardt, H., Liebner, S., and Wolburg, H. (1996). The pecten oculi of the chicken as a new in vivo model of the blood-brain barrier. Cell Tissue Res. 285:91–100.PubMedGoogle Scholar
  41. Giepmans, B. N. G., and Moolenaar, W. H. (1998). The gap junction protein connexin43 interacts with the second PDZ domain of the zona occludens-1 protein. Curr. Biol. 8:931–934.PubMedGoogle Scholar
  42. Gonzales-Mariscal, L., Chavez de Ramirez, B., and Cereijido, M. (1985). Tight junction formation in cultured epithelial cells (MDCK). J. Membr. Biol. 86:113–121.PubMedGoogle Scholar
  43. Gonzales-Mariscal, L., Contreras, R. G., Bolivar, J. J., Ponce, A., Chavez de Ramirez, B., and Cerijido, M. (1990). The role of calcium in tight junction formation between epithelial cells. Am. J. Physiol. 259:C978-C986.PubMedGoogle Scholar
  44. Grebenkämper, K., and Galla, H.-J. (1994). Translational diffusion measurements of a fluorescent phospholipid between MDCK-1 cells support the lipid model of the tight junctions. Chem. Phys. Lipids 71:133–143.PubMedGoogle Scholar
  45. Griepp, E. B., Dolan, W. J., Robbins, E. S., and Sabatini, D. D. (1983). Participation of plasma membrane proteins in the formation of tight junctions by cultured epithelial cells. J. Cell Biol. 96:693–702.PubMedGoogle Scholar
  46. Gumbiner, B., and Simons, K. (1986). A functional assay for proteins involved in establishing an epithelial occluding barrier: Identification of an uvomorulin-like polypeptide. J. Cell Biol. 102:457–468.PubMedGoogle Scholar
  47. Gumbiner, B., Stevenson, B., and Grimaldi, A. (1988). The role of the cell adhesion molecule uvomorulin in the formation and maintenance of the epithelial junctional complex. J. Cell Biol. 107:1575–1587.PubMedGoogle Scholar
  48. Haskins, J, Gu, L., Wittchen, E. S., Hibbard, J., and Stevenson, B. R. (1998). ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin. J. Cell Biol. 141:199–208.PubMedGoogle Scholar
  49. Hein, M., Madefessel, C., Haag, B., Teichmann, K., Post, A., and Galla, H. (1992). Reversible modulation of transepithelial resistance in high and low resistance MDCK-cells by basic amino acids, Ca2+, protamine and protons. Chem. Phys. Lipids 63:223–233.PubMedGoogle Scholar
  50. Heiss, J. D., Papavassiliou, E., Merril, M. J., Nieman, L., Knightly, J. J., Walbridge, S., Edwards, N. A., and Oldfield, E. H. (1996). Mechanism of dexamethasone suppression of brain tumor-associated vascular permeability in rats. Involvement of the glucocorticoid receptor and vascular permeability factor. J. Clin. Invest. 98:1400–1408.PubMedGoogle Scholar
  51. Hirase, T., Staddon, J. M., Saitou, M., Ando-Akatsuka, Y., Itoh, M., Furuse, M., Fujimoto, K., Tsukita, S., and Rubin, L. L. (1997). Occludin as a possible determinant of tight junction permeability in ECs. J. Cell Sci. 110:1603–1613.PubMedGoogle Scholar
  52. Hirokawa, N. (1982). The intramembrane structure of tight junctions. An experimental analysis of the single-fibril and two-fibrils models using the quick-freeze method. J. Ultrastruct. Res. 80:288–301.PubMedGoogle Scholar
  53. Howarth, A. G., Hughes, M. R., and Stevenson, B. R. (1992). Detection of the tight junction associated protein ZO-1 in astrocytes and other non-epithelial cell types. Am. J. Physiol. 262:C461-C469.PubMedGoogle Scholar
  54. Hüttner, I., and Peters, H. (1978). Heterogenity of cell junctions in rat aortic endothelium. A freeze-fracture study. J. Ultrastruct. Res. 63:303–308.Google Scholar
  55. Isenmann, S., Brandner, S., Kuhne, G., Boner, J., and Aguzzi, A. (1996). Comparative in vivo and pathological analysis of the blood-brain barrier in mouse telencephalic transplants. Neuropathol. Appl. Neurobiol. 22:118–128.PubMedGoogle Scholar
  56. Itoh, M., Nagafuchi, A., Yonemura, S., Kitaniyasuda, T., and 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. 121:491–502.PubMedGoogle Scholar
  57. Itoh, M., Nagafuchi, A., Moroi, S., and Tsukita, S. (1997). Involvement of ZO-1 in cadherin-based cell adhesion through its direct binding to a-catenin and actin filaments. J. Cell Biol. 138:181–192.PubMedGoogle Scholar
  58. Jesaitis, L. A., and Goodenough, D. A. (1994). Molecular characterization and tissue distribution of ZO-2, a tight junction protein homologous to ZO-1 and the Drosophila discs-large tumor suppressor protein. J. Cell Biol. 124:949–962.PubMedGoogle Scholar
  59. Johanson, C. E. (1980). Permeability and vascularity of the developing brain: Cerebellum vs. cerebral cortex. Brain Res. 190:3–16.PubMedGoogle Scholar
  60. Jou, T.-S., Schneeberger, E. E., and Nelson, W. J. (1998). Structural and functional regulation of tight junctions by rhoA and rac1 small GTPases. J. Cell Biol. 142:101–115.PubMedGoogle Scholar
  61. Kemler, R. (1993). From cadherins to catenins:cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet. 9:317–332.PubMedGoogle Scholar
  62. Keon, B. H., Schäfer, S., Kuhn, C., Grund, C., and Franke, W. W. (1996). Symplekin, a novel type of tight junction plaque protein. J. Cell Biol. 134:1003–1018.PubMedGoogle Scholar
  63. Kniesel, U., and Wolburg, H. (1993). Tight junction complexity in the retinal pigment epithelium of the chicken during development. Neurosci. Lett. 149:71–74.PubMedGoogle Scholar
  64. Kniesel, U., Risau, W., and Wolburg, H. (1996). Development of blood-brain barrier tight junctions in the rat cortex. Dev. Brain Res. 96:229–240.Google Scholar
  65. Kovbasnjuk, O. N., Szmulowicz, U., and Spring, K. R. (1998) Regulation of the MDCK tight junction. J. Membr. Biol. 161:93–104.PubMedGoogle Scholar
  66. Kurihara, H., Anderson, J. M., and Farquhar, M. G. (1992). Diversity among tight junctions in rat kidney. Glomerular slit diaphragms and endothelial junctions express only one isoform of the tight junction protein ZO-1. Proc. Natl. Acad. Sci. USA 89:7075–7079.PubMedGoogle Scholar
  67. Lane, N. J., Reese, T. J., and Kachar, B. (1992). Structural domains of the tight junctional intramembrane fibrils. Tissue Cell 24:291–300.PubMedGoogle Scholar
  68. Lue, R., Marfatia, S. M., Branton, D., and Chishti, A. H. (1994). Cloning and characterization of hdlg: The human homologue of the Drosophila disc large tumor suppressor binds to protein 4.1. Proc. Natl. Acad. Sci. USA 91:9818–9822.PubMedGoogle Scholar
  69. Mack, A., Neuhaus, J., and Wolburg, H. (1987). Relationship between orthogonal arrays of particles and tight junctions as demonstrated in cells of the ventricular wall of the rat brain. Cell Tissue Res. 248:619–625.PubMedGoogle Scholar
  70. Madara, J. L. (1998). Regulation of the movement of solutes across tight junctions. Annu. Rev. Physiol. 60:143–159.PubMedGoogle Scholar
  71. Madara, J. L., and Dharmasathaphorn, K. (1985). Occluding junction structure-function relationships in a cultured epithelial monolayer. J. Cell Biol. 101:2124–2133.PubMedGoogle Scholar
  72. Madara, J. L., Barenberg, D., and Carlson, S. (1986). Effects of cytochalasin D on occluding junctions of intestinal absorptive cells: Further evidence that the cytoskeleton may influence paracellular permeability and junctional charge selectivity. J. Cell Biol. 102:2125–2136.PubMedGoogle Scholar
  73. Mandel, L. J., Bacallao, R., and Zampighi, G. (1993). Uncoupling of the molecular “fence” and paracellular “gate” functions in epithelial tight junctions. Nature 361:552–555.PubMedGoogle Scholar
  74. Marcial, M. A., Carlson, S. L., and Madara, J. L. (1984). Partitioning of paracellular conductance along the ileal crypt-villus axis: A hypothesis based on structural analysis with detailed consideration of tight junction structure-function relationship. J. Membr. Biol. 80:59–70.PubMedGoogle Scholar
  75. Martinez-Palomo, A., Meza, I., Beaty, G., and Cereijido, M. (1980). Experimental modulation of occluding junctions in a cultured transporting epithelium. J. Cell Biol. 87:736–745.PubMedGoogle Scholar
  76. Matter, K., and Balda, M. S. (1998). Biogenesis of tight junctions: The c-terminal domain of occludin mediates basolateral targeting. J. Cell Sci. 111:511–519.PubMedGoogle Scholar
  77. McCarthy, K. M., Skare, I. B., Stankewich, M. C., Furuse, M., Tsukita, S., Rogers, R. A., Lynch, R. D., and Schneeberger, E. E. (1996). Occludin is a functional component of the tight junction. J. Cell Sci. 109:2287–2298.PubMedGoogle Scholar
  78. Méresse, S., Dehonk, M.-P., Delorme, P., Bensaid, M., Tauber, J.-P., Delbart, C., Fruchart, J.-C., and Cecchelli, R. (1989). Bovine brain ECs express tight junctions and monoamine oxidase activity in long-term culture. J. Neurochem. 53:1363–1371.PubMedGoogle Scholar
  79. Meza, I., Ibarra, G., Sabanero, M., Martinez-Palomo, A., and Cereijido, M. (1980). Occluding junctions and cytoskeletal components in a cultured transporting epithelium. J. Cell Biol. 87:746–754.PubMedGoogle Scholar
  80. Millauer, B., Shawver, L. K., Plate, K. H., Risau, W., and Ullrich, A. (1994). Glioblastoma growth inhibited in vivo by a dominant-negative flk-1 mutant. Nature 367:576–579.PubMedGoogle Scholar
  81. Mitic, L. L., and Anderson, J. M. (1998). Molecular architecture of tight junctions. Annu. Rev. Physiol. 60:121–142.PubMedGoogle Scholar
  82. Møllgård, K., and Saunders, N. R. (1986). The development of the human blood-brain and blood-CSF barriers. Neuropathol. Appl. Neurobiol. 12:337–358.PubMedGoogle Scholar
  83. Moolenaar, W. H. (1995). Lysophosphatidic acid: A multifunctional phospholipid messenger. J. Biol. Chem. 270:12949–12952.PubMedGoogle Scholar
  84. Nabeshima, S., Reese, T. S., Landis, D. M., and Brightman, M. W. (1975). Junctions in the meninges and marginal glia. J. Comp. Neurol. 164:127–170.PubMedGoogle Scholar
  85. Nagy, Z., Peters, H., and Hüttner, I. (1984). Fracture faces of cell junctions in cerebral endothelium during normal and hyperosmotic conditions. Lab. Invest. 50:313–322.PubMedGoogle Scholar
  86. Nico, B., Cantino, D., Bertossi, M., Ribatti, D., Sassoe, M., and Roncali, L. (1992). Tight endothelial junctions in the developing microvasculature. A thin section and freeze-fracture study in the chick embryo optic tectum. J. Submicrosc. Cytol. Pathol. 24:85–96.PubMedGoogle Scholar
  87. Noske, W., and Hirsch, M. (1986). Morphology of tight junctions in the ciliary epithelium of rabbits during arachidonic acid-induced breakdown of the blood-aqueous barrier. Cell Tissue Res. 245:405–412.PubMedGoogle Scholar
  88. Nusrat, A., Giry, M., Turner, J. R., Colgan, S. P., Parkos, D., Lemichez, E., Boquet, P., and Madara, J. L. (1995). Rho protein regulates tight junctions and perijunctional actin organization in polarized epithelia. Proc. Natl. Acad. Sci. USA 92:10629–10633.PubMedGoogle Scholar
  89. Rajasekaran, A. K., Hojo, M., Huima, T., and Rodriguez-Boulan, E. (1996). Catenins and zonula occludens-1 form a complex during early stages in the assembly of tight junctions. J. Cell Biol. 132:451–464.PubMedGoogle Scholar
  90. Rascher, G., and Wolburg, H. (1997). The tight junctions of the leptomeningeal blood-cerebrospinal fluid barrier during development. J. Brain Res. 38:525–540.Google Scholar
  91. Reese, T. S., and Karnovsky, M. J. (1967). Fine structural localization of a blood-brain barrier to exogenous peroxidase. J. Cell Biol. 34:207–217.PubMedGoogle Scholar
  92. Rubin, L. L., Hall, D. E., Porter, S., Barbu, K., Cannon, C., Horner, H. C., Janatpour, M., Liaw, C. W., Manning, K., Morales, J., Tanner, L. J., Tomaselli, K. J., and Bard, F. (1991). A cell culture model of the blood-brain barrier. J. Cell Biol. 115:1725–1736.Google Scholar
  93. Saitou, M., Ando-Akatsuka, Y., Itoh, M., Furuse, M., Inazawa, J., Fujimoto, K., and Tsukita, S. (1997). Mammalian occludin in epithelial cells: Its expression and subcellular distribution. Eur. J. Cell Biol. 73:222–231.PubMedGoogle Scholar
  94. Saitou, M., Fujimoto, K., Doi, Y., Fujimoto, T., Furuse, M., Takano, H., Noda, T., and Tsukita, S. (1998). Occludin-deficient embryonic stem cells can differentiate into polarized epithelial cells bearing tight junctions. J. Cell Biol. 141:397–408.PubMedGoogle Scholar
  95. Sakakibara, A., Furuse, M., Saitou, M., Ando-Akatsuka, Y., and Tsukita, S. (1997). Possible involvement of phosphorylation of occludin in tight junction formation. J. Cell Biol. 137: 1393–1401.PubMedGoogle Scholar
  96. Sandri, C., Akert, K., and Bennett, M. V. L. (1978). Junctional complexes and variations in gap junctions between spinal cord ependymal cells of a teleost, Sternarchus albifrons (Gymnotoidae). Brain Res. 143:27–41.PubMedGoogle Scholar
  97. Satoh, H., Zhong, Y., Isomura, H., Saitoh, M., Enomoto, K., Sawada, N., and Mori, M. (1996). Localization of 7H6 tight junction-associated antigen along the cell border of vascular ECs correlates with paracellular barrier function against ions, large molecules, and cancer cells. Exp. Cell Res. 222:269–274.PubMedGoogle Scholar
  98. Schulze, C., and Firth, J. A. (1992). Interendothelial junctions during blood-brain barrier development in the rat. Morphological changes at the level of individual tight junctional contacts. Dev. Brain Res. 69:85–96.Google Scholar
  99. Schulze, C., and Firth, J. A. (1993). Immunohistochemical localization of adherens junction components in blood-brain barrier microvessels of the rat. J. Cell Sci. 104:773–782.PubMedGoogle Scholar
  100. Schulze, C., Smales, C., Rubin, L. L., and Staddon, J. M. (1997). Lysophophatidic acid increases tight junctional permeability in cultured brain ECs. J. Neurochem. 68:991–1000.PubMedGoogle Scholar
  101. Shivers, R. R. (1979). The blood-brain barrier of a reptile, Anolis carolinensis. A freeze-fracture study. Brain Res. 169:221–230.PubMedGoogle Scholar
  102. Simionescu, M., Simionescu, N., and Palade, G. E. (1976). Segmental differentiations of cell junctions in the vascular endothelium. Arteries and veins. J. Cell Biol. 68:705–723.PubMedGoogle Scholar
  103. Staddon, J. M., and Rubin, L. L. (1996). Cell adhesion, cell junctions and the blood-brain barrier. Curr. Op in. Neurobiol. 6:622–627.Google Scholar
  104. Staddon, J. M., Herrenknecht, K., Smales, C., and Rubin, L. L. (1995). Evidence that tyrosine phosphorylation may increase tight junction permeability. J. Cell Sci. 108:609–619.PubMedGoogle Scholar
  105. Stevenson, B. R., and Begg, D. A. (1994). Concentration-dependent effects of cytochalasin D on tight junctions and actin filaments in MDCK epithelial cells. J. Cell Sci. 107:367–375.PubMedGoogle Scholar
  106. Stevenson, B. R., Siliciano, J. D., Mooseker, M. S., and Goodenough, D. A., (1986). Identification of ZO-1: A higher molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia. J. Cell Biol. 103:755–766.PubMedGoogle Scholar
  107. Stevenson, B. R., Anderson, J. M., Goodenough, D. A. and Mooseker, M. S. (1988). Tight junction structure and ZO-1 content are identical in two strains of Madin-Darby canine kidney cells. J. Cell Biol. 107:2401–2408.PubMedGoogle Scholar
  108. Stewart, P. A., and Hayakawa, E. M. (1987). Interendothelial junctional changes underlie the developmental “tightening” of the blood-brain barrier. Dev. Brain Res. 32:271–281.Google Scholar
  109. Stewart, P. A., and Hayakawa, K. (1994). Early ultrastructural changes in blood-brain barrier vessels of the rat embryo. Dev. Brain Res. 78:25–34.Google Scholar
  110. Stuart, R. O., and Nigam, S. K. (1995). Regulated assembly of tight junctions by protein kinase C. Proc. Natl. Acad. Sci. USA 92:6072–6076.PubMedGoogle Scholar
  111. Stuart, R. O., Sun, A., Panichas, M., Hebert, S. C., Brenner, B. M., and Nigam, S. K. (1994). Critical role for intracellular calcium in tight junction biogenesis. J. Cell. Physiol. 159:423–433.PubMedGoogle Scholar
  112. Suzuki, F., and Nagano, T. (1991). Three-dimensional model of tight junction fibrils based on freeze-fracture images. Cell Tissue Res. 264:381–384.PubMedGoogle Scholar
  113. Takeda, H., and Tsukita, S. (1995). Effects of tyrosine phosphorylation on tight junctions in temperature-sensitive v-src-transfected MDCK. Cell Struct. Funct. 20:387–393.PubMedGoogle Scholar
  114. Tao-Cheng, J.-H., Nagy, Z., and Brightman, M. W. (1987). Tight junctions of brain endothelium in vitro are enhanced by astroglia. J. Neurosci. 7:3293–3299.PubMedGoogle Scholar
  115. Tontsch, U., and Bauer, H. C. (1991). Glial cells and neurons induce blood brain barrier related enzymes in cultured cerebral ECs. Brain Res. 539:247–253.PubMedGoogle Scholar
  116. Van Deurs, B., and Koehler, J. K. (1979). Tight junctions in the choroid plexus epithelium. A freeze-fracture study including complementary replicas. J. Cell Biol. 80:662–673.PubMedGoogle Scholar
  117. Van Itallie, C. M., and Anderson, J. M. (1997). Occludin confers adhesiveness when expressed in fibroblasts. J. Cell Sci. 110:1113–1121.PubMedGoogle Scholar
  118. Van Itallie, C. M., Balda, M. S., and Anderson, J. M. (1995). Epidermal growth factor induces tyrosine phosphorylation and reorganization of the tight junction protein ZO-1 in A431 cells. J. Cell Sci. 108:1735–1742.PubMedGoogle Scholar
  119. Van meer, G., and Simons, K. (1986). The function of tight junctions in maintaining differences in lipid composition between the apical and the basolateral cell surface domains of MDCK cells. EMBO J. 5:1455–zz1464.PubMedGoogle Scholar
  120. Van Meer, G., Gumbiner, B., and Simons, K. (1986). The tight junction does not allow lipid molecules to diffuse from one epithelial cell to the next. Nature 322:639–641.PubMedGoogle Scholar
  121. Wakai, S., and Hirokawa, N. (1978). Development of the blood-brain barrier to horseradish peroxidase in the chick embryo. Cell Tissue Res. 195:195–203.PubMedGoogle Scholar
  122. Willott, E., Balda, M. S., Heintzelman, M., Jameson, B., and Anderson, J. M. (1992). Localization and differential expression of two isoforms of the tight junction protein ZO-1. Am. J. Physiol. 262:C1119-C1124.PubMedGoogle Scholar
  123. Willott, E., Balda, M. S., Fanning, A. S., Jameson, B., Van Itallie, C., and Anderson, J. M. (1993). The tight junction protein ZO-1 is homologus to the Drosophila discs-large tumor suppressor protein of septate junctions. Proc. Natl. Acad. Sci. USA 90:7834–7838.PubMedGoogle Scholar
  124. Wolburg, H., and Risau, W. (1995). Formation of the blood-brain barrier. In Kettenmann, H., and Ransom B. R. (eds.), Neuroglia, Oxford University Press, New York, Oxford, pp. 763–776.Google Scholar
  125. Wolburg, H., Kästner, R., and Kurz-Isler, G. (1983). Lack of orthogonal particle assemblies and presence of tight junctions in astrocytes of goldfish. A freeze-fracture study. Cell Tissue Res. 234:389–402.PubMedGoogle Scholar
  126. Wolburg, H., Neuhaus, J., Kniesel, U., Krauss, B., Schmid, E.-M., Öcalan, M. Farrell, C., and Risau, W. (1994). Modulation of tight junction structure in blood-brain barrier ECs. Effects of tissue culture, second messengers and cocultured astrocytes. J. Cell Sci. 107:1347–1357.Google Scholar
  127. Wong, V., and Gumbiner, B. M. (1997). A synthetic peptide corresponding to the extracellular domain of occludin perturbs the tight junction permeability barrier. J. Cell Biol. 136:399–409.PubMedGoogle Scholar
  128. Woods, D. F., and Bryant, P. J. (1991). The disc large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions. Cell 66:451–464.PubMedGoogle Scholar
  129. Zhong, Y., Enomoto, K., Isomura, H., Sawada, N., Minase, T., Oyamada, M., Konishi, Y., and Mori, M. (1994). Localization of the 7H6 antigen at tight junctions correlates with the paracellular barrier function of MDCK cells. Exp. Cell Res. 214:614–620.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 2000

Authors and Affiliations

  • Uwe Kniesel
    • 1
  • Hartwig Wolburg
    • 1
  1. 1.Institute of PathologyUniversity of TübingenTübingenGermany

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