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Tight junction proteins at the blood–brain barrier: far more than claudin-5

  • Philipp Berndt
  • Lars WinklerEmail author
  • Jimmi Cording
  • Olga Breitkreuz-Korff
  • André Rex
  • Sophie Dithmer
  • Valentina Rausch
  • Rosel Blasig
  • Matthias Richter
  • Anje Sporbert
  • Hartwig Wolburg
  • Ingolf E. Blasig
  • Reiner F. HaseloffEmail author
Original Article
  • 60 Downloads

Abstract

At the blood–brain barrier (BBB), claudin (Cldn)-5 is thought to be the dominant tight junction (TJ) protein, with minor contributions from Cldn3 and -12, and occludin. However, the BBB appears ultrastructurally normal in Cldn5 knock-out mice, suggesting that further Cldns and/or TJ-associated marvel proteins (TAMPs) are involved. Microdissected human and murine brain capillaries, quickly frozen to recapitulate the in vivo situation, showed high transcript expression of Cldn5, -11, -12, and -25, and occludin, but also abundant levels of Cldn1 and -27 in man. Protein levels were quantified by a novel epitope dilution assay and confirmed the respective mRNA data. In contrast to the in vivo situation, Cldn5 dominates BBB expression in vitro, since all other TJ proteins are at comparably low levels or are not expressed. Cldn11 was highly abundant in vivo and contributed to paracellular tightness by homophilic oligomerization, but almost disappeared in vitro. Cldn25, also found at high levels, neither tightened the paracellular barrier nor interconnected opposing cells, but contributed to proper TJ strand morphology. Pathological conditions (in vivo ischemia and in vitro hypoxia) down-regulated Cldn1, -3, and -12, and occludin in cerebral capillaries, which was paralleled by up-regulation of Cldn5 after middle cerebral artery occlusion in rats. Cldn1 expression increased after Cldn5 knock-down. In conclusion, this complete Cldn/TAMP profile demonstrates the presence of up to a dozen TJ proteins in brain capillaries. Mouse and human share a similar and complex TJ profile in vivo, but this complexity is widely lost under in vitro conditions.

Keywords

Brain endothelium Ischemia Protein–protein interaction Laser capture microdissection Neurovasculature 

Abbreviations

BBB

Blood–brain barrier

BSA

Bovine serum albumin

CFP

Cyan fluorescent protein

Cldn

Claudin

CRFR

Corticotrophin-releasing factor receptor

DMEM

Dulbecco’s modified Eagle’s medium

EDTA

Ethylenediaminetetraacetic acid

FCS

Fetal calf serum

FRET

Fluorescence resonance energy transfer

HB-EGF

Heparin-binding epidermal growth factor-like growth factor

HEK

Human embryonic kidney

MBP

Maltose-binding protein

MCAO

Middle cerebral artery occlusion

MDCK

Madin–Darby canine kidney cells

MRI

Magnetic resonance imaging

Ocln

Occludin

PBS

Phosphate buffered saline

PEI

Polyethylenimine

qRT-PCR

Quantitative real-time polymerase chain reaction

RCA1

Ricinus communis agglutinin

SDS-PAGE

Sodium dodecyl sulfate polyacryl gel electrophoresis

TAMP

Tight junction-associated Marvel protein

TER

Transcellular electrical resistance

TJ

Tight junction

TX-100

Triton X-100

VEGF

Vascular endothelial growth factor

YFP

Yellow fluorescent protein

Notes

Acknowledgements

The authors wish to thank Michael Krauss (FMP Berlin) for help in lentiviral preparation, Susanne Müller (Charité Universitätsmedizin Berlin, Dept. Experimental Neurology) for help in MRI experiments and Ria Knittel (University Hospital, Tübingen, Dept. Pathology and Neuropathology) for skillful assistance with the freeze-fracture technology.

Supplementary material

18_2019_3030_MOESM1_ESM.pdf (641 kb)
Supplementary material 1 (PDF 641 kb)

References

  1. 1.
    Krause G, Winkler L, Mueller SL, Haseloff RF, Piontek J, Blasig IE (2008) Structure and function of claudins. Biochim Biophys Acta 1778(3):631–645.  https://doi.org/10.1016/j.bbamem.2007.10.018 Google Scholar
  2. 2.
    Haseloff RF, Dithmer S, Winkler L, Wolburg H, Blasig IE (2015) Transmembrane proteins of the tight junctions at the blood–brain barrier: structural and functional aspects. Semin Cell Dev Biol 38:16–25.  https://doi.org/10.1016/j.semcdb.2014.11.004 Google Scholar
  3. 3.
    Maher GJ, Hilton EN, Urquhart JE, Davidson AE, Spencer HL, Black GC, Manson FD (2011) The cataract-associated protein TMEM114, and TMEM235, are glycosylated transmembrane proteins that are distinct from claudin family members. FEBS Lett 585(14):2187–2192.  https://doi.org/10.1016/j.febslet.2011.05.060 Google Scholar
  4. 4.
    Mineta K, Yamamoto Y, Yamazaki Y, Tanaka H, Tada Y, Saito K, Tamura A, Igarashi M, Endo T, Takeuchi K, Tsukita S (2011) Predicted expansion of the claudin multigene family. FEBS Lett 585(4):606–612.  https://doi.org/10.1016/j.febslet.2011.01.028 Google Scholar
  5. 5.
    Cording J, Berg J, Kading N, Bellmann C, Tscheik C, Westphal JK, Milatz S, Gunzel D, Wolburg H, Piontek J, Huber O, Blasig IE (2013) In tight junctions, claudins regulate the interactions between occludin, tricellulin and marvelD3, which, inversely, modulate claudin oligomerization. J Cell Sci 126(Pt 2):554–564.  https://doi.org/10.1242/jcs.114306 Google Scholar
  6. 6.
    Piontek J, Fritzsche S, Cording J, Richter S, Hartwig J, Walter M, Yu D, Turner JR, Gehring C, Rahn HP, Wolburg H, Blasig IE (2011) Elucidating the principles of the molecular organization of heteropolymeric tight junction strands. Cell Mol Life Sci 68(23):3903–3918.  https://doi.org/10.1007/s00018-011-0680-z Google Scholar
  7. 7.
    Gunzel D, Yu AS (2013) Claudins and the modulation of tight junction permeability. Physiol Rev 93(2):525–569.  https://doi.org/10.1152/physrev.00019.2012 Google Scholar
  8. 8.
    Capaldo CT, Nusrat A (2015) Claudin switching: physiological plasticity of the tight junction. Semin Cell Dev Biol 42:22–29.  https://doi.org/10.1016/j.semcdb.2015.04.003 Google Scholar
  9. 9.
    Gupta IR, Ryan AK (2010) Claudins: unlocking the code to tight junction function during embryogenesis and in disease. Clin Genet 77(4):314–325.  https://doi.org/10.1111/j.1399-0004.2010.01397.x Google Scholar
  10. 10.
    Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ (2010) Structure and function of the blood–brain barrier. Neurobiol Dis 37(1):13–25.  https://doi.org/10.1016/j.nbd.2009.07.030 Google Scholar
  11. 11.
    Ohtsuki S, Sato S, Yamaguchi H, Kamoi M, Asashima T, Terasaki T (2007) Exogenous expression of claudin-5 induces barrier properties in cultured rat brain capillary endothelial cells. J Cell Physiol 210(1):81–86.  https://doi.org/10.1002/jcp.20823 Google Scholar
  12. 12.
    Nitta T, Hata M, Gotoh S, Seo Y, Sasaki H, Hashimoto N, Furuse M, Tsukita S (2003) Size-selective loosening of the blood–brain barrier in claudin-5-deficient mice. J Cell Biol 161(3):653–660.  https://doi.org/10.1083/jcb.200302070 Google Scholar
  13. 13.
    Ohtsuki S, Yamaguchi H, Katsukura Y, Asashima T, Terasaki T (2008) mRNA expression levels of tight junction protein genes in mouse brain capillary endothelial cells highly purified by magnetic cell sorting. J Neurochem 104(1):147–154.  https://doi.org/10.1111/j.1471-4159.2007.05008.x Google Scholar
  14. 14.
    Daneman R, Zhou L, Agalliu D, Cahoy JD, Kaushal A, Barres BA (2010) The mouse blood–brain barrier transcriptome: a new resource for understanding the development and function of brain endothelial cells. PLoS One 5(10):e13741.  https://doi.org/10.1371/journal.pone.0013741 Google Scholar
  15. 15.
    Kooij G, Kopplin K, Blasig R, Stuiver M, Koning N, Goverse G, van der Pol SM, van Het Hof B, Gollasch M, Drexhage JA, Reijerkerk A, Meij IC, Mebius R, Willnow TE, Muller D, Blasig IE, de Vries HE (2014) Disturbed function of the blood–cerebrospinal fluid barrier aggravates neuro-inflammation. Acta Neuropathol 128(2):267–277.  https://doi.org/10.1007/s00401-013-1227-1 Google Scholar
  16. 16.
    Bocsik A, Walter FR, Gyebrovszki A, Fulop L, Blasig I, Dabrowski S, Otvos F, Toth A, Rakhely G, Veszelka S, Vastag M, Szabo-Revesz P, Deli MA (2016) Reversible opening of intercellular junctions of intestinal epithelial and brain endothelial cells with tight junction modulator peptides. J Pharm Sci 105(2):754–765.  https://doi.org/10.1016/j.xphs.2015.11.018 Google Scholar
  17. 17.
    Uchida Y, Sumiya T, Tachikawa M, Yamakawa T, Murata S, Yagi Y, Sato K, Stephan A, Ito K, Ohtsuki S, Couraud PO, Suzuki T, Terasaki T (2018) Involvement of claudin-11 in disruption of blood–brain, –spinal cord, and –arachnoid barriers in multiple sclerosis. Mol Neurobiol.  https://doi.org/10.1007/s12035-018-1207-5 Google Scholar
  18. 18.
    Taddei A, Giampietro C, Conti A, Orsenigo F, Breviario F, Pirazzoli V, Potente M, Daly C, Dimmeler S, Dejana E (2008) Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5. Nat Cell Biol 10(8):923–934.  https://doi.org/10.1038/ncb1752 Google Scholar
  19. 19.
    Huang J, Li J, Qu Y, Zhang J, Zhang L, Chen X, Liu B, Zhu Z (2014) The expression of claudin 1 correlates with beta-catenin and is a prognostic factor of poor outcome in gastric cancer. Int J Oncol 44(4):1293–1301.  https://doi.org/10.3892/ijo.2014.2298 Google Scholar
  20. 20.
    Liebner S, Corada M, Bangsow T, Babbage J, Taddei A, Czupalla CJ, Reis M, Felici A, Wolburg H, Fruttiger M, Taketo MM, von Melchner H, Plate KH, Gerhardt H, Dejana E (2008) Wnt/beta-catenin signaling controls development of the blood–brain barrier. J Cell Biol 183(3):409–417.  https://doi.org/10.1083/jcb.200806024 Google Scholar
  21. 21.
    Dorfel MJ, Huber O (2012) Modulation of tight junction structure and function by kinases and phosphatases targeting occludin. J Biomed Biotechnol 2012:807356.  https://doi.org/10.1155/2012/807356 Google Scholar
  22. 22.
    Titchenell PM, Lin CM, Keil JM, Sundstrom JM, Smith CD, Antonetti DA (2012) Novel atypical PKC inhibitors prevent vascular endothelial growth factor-induced blood–retinal barrier dysfunction. Biochem J 446(3):455–467.  https://doi.org/10.1042/BJ20111961 Google Scholar
  23. 23.
    Murakami T, Frey T, Lin CM, Antonetti DA (2012) Protein kinase C beta phosphorylates occludin regulating tight junction trafficking in vascular endothelial growth factor-induced permeability in vivo. Diabetes 61(6):1573–1583.  https://doi.org/10.2337/db11-1367 Google Scholar
  24. 24.
    Daneman R, Prat A (2015) The blood–brain barrier. Cold Spring Harb Perspect Biol 7(1):a020412.  https://doi.org/10.1101/cshperspect.a020412 Google Scholar
  25. 25.
    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 27(4):697–709.  https://doi.org/10.1038/sj.jcbfm.9600375 Google Scholar
  26. 26.
    Teng F, Beray-Berthat V, Coqueran B, Lesbats C, Kuntz M, Palmier B, Garraud M, Bedfert C, Slane N, Berezowski V, Szeremeta F, Hachani J, Scherman D, Plotkine M, Doan BT, Marchand-Leroux C, Margaill I (2013) Prevention of rt-PA induced blood–brain barrier component degradation by the poly(ADP-ribose)polymerase inhibitor PJ34 after ischemic stroke in mice. Exp Neurol 248:416–428.  https://doi.org/10.1016/j.expneurol.2013.07.007 Google Scholar
  27. 27.
    Zhang H, Ren C, Gao X, Takahashi T, Sapolsky RM, Steinberg GK, Zhao H (2008) Hypothermia blocks beta-catenin degradation after focal ischemia in rats. Brain Res 1198:182–187.  https://doi.org/10.1016/j.brainres.2008.01.007 Google Scholar
  28. 28.
    Brown RC, Mark KS, Egleton RD, Huber JD, Burroughs AR, Davis TP (2003) Protection against hypoxia-induced increase in blood–brain barrier permeability: role of tight junction proteins and NFkappaB. J Cell Sci 116(Pt 4):693–700.  https://doi.org/10.1242/jcs.00264 Google Scholar
  29. 29.
    Li L, McBride DW, Doycheva D, Dixon BJ, Krafft PR, Zhang JH, Tang J (2015) G-CSF attenuates neuroinflammation and stabilizes the blood–brain barrier via the PI3K/Akt/GSK-3beta signaling pathway following neonatal hypoxia–ischemia in rats. Exp Neurol 272:135–144.  https://doi.org/10.1016/j.expneurol.2014.12.020 Google Scholar
  30. 30.
    Bellmann C, Schreivogel S, Gunther R, Dabrowski S, Schumann M, Wolburg H, Blasig IE (2014) Highly conserved cysteines are involved in the oligomerization of occludin-redox dependency of the second extracellular loop. Antioxid Redox Signal 20(6):855–867.  https://doi.org/10.1089/ars.2013.5288 Google Scholar
  31. 31.
    Cording J, Gunther R, Vigolo E, Tscheik C, Winkler L, Schlattner I, Lorenz D, Haseloff RF, Schmidt-Ott KM, Wolburg H, Blasig IE (2015) Redox regulation of cell contacts by tricellulin and occludin: redox-sensitive cysteine sites in tricellulin regulate both tri- and bicellular junctions in tissue barriers as shown in hypoxia and ischemia. Antioxid Redox Signal 23(13):1035–1049.  https://doi.org/10.1089/ars.2014.6162 Google Scholar
  32. 32.
    Blasig IE, Bellmann C, Cording J, del Vecchio G, Zwanziger D, Huber O, Haseloff RF (2011) Occludin protein family: oxidative stress and reducing conditions. Antioxid Redox Signal 15(5):1195–1219.  https://doi.org/10.1089/ars.2010.3542 Google Scholar
  33. 33.
    Castro V, Bertrand L, Luethen M, Dabrowski S, Lombardi J, Morgan L, Sharova N, Stevenson M, Blasig IE, Toborek M (2016) Occludin controls HIV transcription in brain pericytes via regulation of SIRT-1 activation. FASEB J 30(3):1234–1246.  https://doi.org/10.1096/fj.15-277673 Google Scholar
  34. 34.
    Engel O, Kolodziej S, Dirnagl U, Prinz V (2011) Modeling stroke in mice—middle cerebral artery occlusion with the filament model. J Vis Exp.  https://doi.org/10.3791/2423 Google Scholar
  35. 35.
    Mojsilovic-Petrovic J, Nesic M, Pen A, Zhang W, Stanimirovic D (2004) Development of rapid staining protocols for laser-capture microdissection of brain vessels from human and rat coupled to gene expression analyses. J Neurosci Methods 133(1–2):39–48.  https://doi.org/10.1016/j.jneumeth.2003.09.026 Google Scholar
  36. 36.
    Del Vecchio G, Tscheik C, Tenz K, Helms HC, Winkler L, Blasig R, Blasig IE (2012) Sodium caprate transiently opens claudin-5-containing barriers at tight junctions of epithelial and endothelial cells. Mol Pharm 9(9):2523–2533.  https://doi.org/10.1021/mp3001414 Google Scholar
  37. 37.
    Haseloff RF, Krause E, Bigl M, Mikoteit K, Stanimirovic D, Blasig IE (2006) Differential protein expression in brain capillary endothelial cells induced by hypoxia and posthypoxic reoxygenation. Proteomics 6(6):1803–1809.  https://doi.org/10.1002/pmic.200500182 Google Scholar
  38. 38.
    Zwanziger D, Staat C, Andjelkovic AV, Blasig IE (2012) Claudin-derived peptides are internalized via specific endocytosis pathways. Ann N Y Acad Sci 1257:29–37.  https://doi.org/10.1111/j.1749-6632.2012.06567.x Google Scholar
  39. 39.
    Untergasser A, Cutcutache I, Koressaar T, Ye J, Faircloth BC, Remm M, Rozen SG (2012) Primer3-new capabilities and interfaces. Nucleic Acids Res 40(15):e115.  https://doi.org/10.1093/nar/gks596 Google Scholar
  40. 40.
    Schmidt A, Utepbergenov DI, Krause G, Blasig IE (2001) Use of surface plasmon resonance for real-time analysis of the interaction of ZO-1 and occludin. Biochem Biophys Res Commun 288(5):1194–1199.  https://doi.org/10.1006/bbrc.2001.5914 Google Scholar
  41. 41.
    Blasig IE, Winkler L, Lassowski B, Mueller SL, Zuleger N, Krause E, Krause G, Gast K, Kolbe M, Piontek J (2006) On the self-association potential of transmembrane tight junction proteins. Cell Mol Life Sci 63(4):505–514.  https://doi.org/10.1007/s00018-005-5472-x Google Scholar
  42. 42.
    Dabrowski S, Staat C, Zwanziger D, Sauer RS, Bellmann C, Gunther R, Krause E, Haseloff RF, Rittner H, Blasig IE (2015) Redox-sensitive structure and function of the first extracellular loop of the cell–cell contact protein claudin-1: lessons from molecular structure to animals. Antioxid Redox Signal 22(1):1–14.  https://doi.org/10.1089/ars.2013.5706 Google Scholar
  43. 43.
    Piontek J, Winkler L, Wolburg H, Muller SL, Zuleger N, Piehl C, Wiesner B, Krause G, Blasig IE (2008) Formation of tight junction: determinants of homophilic interaction between classic claudins. FASEB J 22(1):146–158.  https://doi.org/10.1096/fj.07-8319com Google Scholar
  44. 44.
    Tiwari-Woodruff S, Beltran-Parrazal L, Charles A, Keck T, Vu T, Bronstein J (2006) K+ channel KV3.1 associates with OSP/claudin-11 and regulates oligodendrocyte development. Am J Physiol Cell Physiol 291(4):C687–C698.  https://doi.org/10.1152/ajpcell.00510.2005 Google Scholar
  45. 45.
    Bronstein JM, Popper P, Micevych PE, Farber DB (1996) Isolation and characterization of a novel oligodendrocyte-specific protein. Neurology 47(3):772–778.  https://doi.org/10.1212/wnl.47.3.772 Google Scholar
  46. 46.
    Morita K, Sasaki H, Fujimoto K, Furuse M, Tsukita S (1999) Claudin-11/OSP-based tight junctions of myelin sheaths in brain and sertoli cells in testis. J Cell Biol 145(3):579–588.  https://doi.org/10.1083/jcb.200110122 Google Scholar
  47. 47.
    Jiao H, Wang Z, Liu Y, Wang P, Xue Y (2011) Specific role of tight junction proteins claudin-5, occludin, and ZO-1 of the blood–brain barrier in a focal cerebral ischemic insult. J Mol Neurosci 44(2):130–139.  https://doi.org/10.1007/s12031-011-9496-4 Google Scholar
  48. 48.
    Weuste M, Wurm A, Iandiev I, Wiedemann P, Reichenbach A, Bringmann A (2006) HB-EGF: increase in the ischemic rat retina and inhibition of osmotic glial cell swelling. Biochem Biophys Res Commun 347(1):310–318.  https://doi.org/10.1016/j.bbrc.2006.06.077 Google Scholar
  49. 49.
    Wolburg H, Wolburg-Buchholz K, Kraus J, Rascher-Eggstein G, Liebner S, Hamm S, Duffner F, Grote EH, Risau W, Engelhardt B (2003) Localization of claudin-3 in tight junctions of the blood–brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme. Acta Neuropathol 105(6):586–592.  https://doi.org/10.1007/s00401-003-0688-z Google Scholar
  50. 50.
    Furuse M, Hata M, Furuse K, Yoshida Y, Haratake A, Sugitani Y, Noda T, Kubo A, Tsukita S (2002) Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J Cell Biol 156(6):1099–1111.  https://doi.org/10.1083/jcb.200110122 Google Scholar
  51. 51.
    Nakano Y, Kim SH, Kim HM, Sanneman JD, Zhang Y, Smith RJ, Marcus DC, Wangemann P, Nessler RA, Banfi B (2009) A claudin-9-based ion permeability barrier is essential for hearing. PLoS Genet 5(8):e1000610.  https://doi.org/10.1371/journal.pgen.1000610 Google Scholar
  52. 52.
    McCabe MJ, Foo CF, Dinger ME, Smooker PM, Stanton PG (2016) Claudin-11 and occludin are major contributors to Sertoli cell tight junction function, in vitro. Asian J Androl 18(4):620–626.  https://doi.org/10.4103/1008-682X.163189 Google Scholar
  53. 53.
    Pardridge WM, Triguero D, Yang J, Cancilla PA (1990) Comparison of in vitro and in vivo models of drug transcytosis through the blood–brain barrier. J Pharmacol Exp Ther 253(2):884–891Google Scholar
  54. 54.
    Kratzer I, Vasiljevic A, Rey C, Fevre-Montange M, Saunders N, Strazielle N, Ghersi-Egea JF (2012) Complexity and developmental changes in the expression pattern of claudins at the blood–CSF barrier. Histochem Cell Biol 138(6):861–879.  https://doi.org/10.1007/s00418-012-1001-9 Google Scholar
  55. 55.
    Liu J, Jin X, Liu KJ, Liu W (2012) Matrix metalloproteinase-2-mediated occludin degradation and caveolin-1-mediated claudin-5 redistribution contribute to blood–brain barrier damage in early ischemic stroke stage. J Neurosci 32(9):3044–3057.  https://doi.org/10.1523/JNEUROSCI.6409-11.2012 Google Scholar
  56. 56.
    Neuhaus W, Gaiser F, Mahringer A, Franz J, Riethmuller C, Forster C (2014) The pivotal role of astrocytes in an in vitro stroke model of the blood–brain barrier. Front Cell Neurosci 8:78.  https://doi.org/10.3389/fncel.2014.00352 Google Scholar
  57. 57.
    Tran KA, Zhang XM, Predescu D, Huang XJ, Machado RF, Gothert JR, Malik AB, Valyi-Nagy T, Zhao YY (2016) Endothelial beta-catenin signaling is required for maintaining adult blood–brain barrier integrity and central nervous system homeostasis. Circulation 133(2):177–186.  https://doi.org/10.1161/circulationaha.115.015982 Google Scholar
  58. 58.
    Chen X, Threlkeld SW, Cummings EE, Juan I, Makeyev O, Besio WG, Gaitanis J, Banks WA, Sadowska GB, Stonestreet BS (2012) Ischemia–reperfusion impairs blood–brain barrier function and alters tight junction protein expression in the ovine fetus. Neuroscience 226:89–100.  https://doi.org/10.1016/j.neuroscience.2012.08.043 Google Scholar
  59. 59.
    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(10):1771–1781Google Scholar
  60. 60.
    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 313(12):2597–2610.  https://doi.org/10.1016/j.yexcr.2007.05.009 Google Scholar
  61. 61.
    Gonzalez-Mariscal L, Quiros M, Diaz-Coranguez M (2011) ZO proteins and redox-dependent processes. Antioxid Redox Signal 15(5):1235–1253.  https://doi.org/10.1089/ars.2011.3913 Google Scholar
  62. 62.
    Morcos Y, Hosie MJ, Bauer HC, Chan-Ling T (2001) Immunolocalization of occludin and claudin-1 to tight junctions in intact CNS vessels of mammalian retina. J Neurocytol 30(2):107–123.  https://doi.org/10.1023/A:1011982906125 Google Scholar
  63. 63.
    Jian Y, Chen C, Li B, Tian X (2015) Delocalized claudin-1 promotes metastasis of human osteosarcoma cells. Biochem Biophys Res Commun 466(3):356–361.  https://doi.org/10.1016/j.bbrc.2015.09.028 Google Scholar
  64. 64.
    French AD, Fiori JL, Camilli TC, Leotlela PD, O’Connell MP, Frank BP, Subaran S, Indig FE, Taub DD, Weeraratna AT (2009) PKC and PKA phosphorylation affect the subcellular localization of claudin-1 in melanoma cells. Int J Med Sci 6(2):93–101.  https://doi.org/10.7150/ijms.6.93 Google Scholar
  65. 65.
    Leotlela PD, Wade MS, Duray PH, Rhode MJ, Brown HF, Rosenthal DT, Dissanayake SK, Earley R, Indig FE, Nickoloff BJ, Taub DD, Kallioniemi OP, Meltzer P, Morin PJ, Weeraratna AT (2007) Claudin-1 overexpression in melanoma is regulated by PKC and contributes to melanoma cell motility. Oncogene 26(26):3846–3856.  https://doi.org/10.1038/sj.onc.1210155 Google Scholar
  66. 66.
    Karnati HK, Panigrahi M, Shaik NA, Greig NH, Bagadi SA, Kamal MA, Kapalavayi N (2014) Down regulated expression of claudin-1 and claudin-5 and up regulation of beta-catenin: association with human glioma progression. CNS Neurol Disord Drug Targets 13(8):1413–1426.  https://doi.org/10.2174/1871527313666141023121550 Google Scholar
  67. 67.
    Wolburg H, Wolburg-Buchholz K, Liebner S, Engelhardt B (2001) Claudin-1, claudin-2 and claudin-11 are present in tight junctions of choroid plexus epithelium of the mouse. Neurosci Lett 307(2):77–80.  https://doi.org/10.1016/s0304-3940(01)01927-9 Google Scholar
  68. 68.
    Gow A, Devaux J (2008) A model of tight junction function in central nervous system myelinated axons. Neuron Glia Biol 4(4):307–317.  https://doi.org/10.1017/S1740925X09990391 Google Scholar
  69. 69.
    Denninger AR, Breglio A, Maheras KJ, LeDuc G, Cristiglio V, Deme B, Gow A, Kirschner DA (2015) Claudin-11 tight junctions in myelin are a barrier to diffusion and lack strong adhesive properties. Biophys J 109(7):1387–1397.  https://doi.org/10.1016/j.bpj.2015.08.012 Google Scholar
  70. 70.
    Gow A, Southwood CM, Li JS, Pariali M, Riordan GP, Brodie SE, Danias J, Bronstein JM, Kachar B, Lazzarini RA (1999) CNS myelin and sertoli cell tight junction strands are absent in Osp/claudin-11 null mice. Cell 99(6):649–659.  https://doi.org/10.1016/S0092-8674(00)81553-6 Google Scholar
  71. 71.
    Hulper P, Veszelka S, Walter FR, Wolburg H, Fallier-Becker P, Piontek J, Blasig IE, Lakomek M, Kugler W, Deli MA (2013) Acute effects of short-chain alkylglycerols on blood–brain barrier properties of cultured brain endothelial cells. Br J Pharmacol 169(7):1561–1573.  https://doi.org/10.1111/bph.12218 Google Scholar
  72. 72.
    Furuse M, Sasaki H, Fujimoto K, Tsukita S (1998) A single gene product, claudin-1 or -2, reconstitutes tight junction strands and recruits occludin in fibroblasts. J Cell Biol 143(2):391–401.  https://doi.org/10.1083/jcb.143.2.391 Google Scholar
  73. 73.
    Dorfel MJ, Westphal JK, Bellmann C, Krug SM, Cording J, Mittag S, Tauber R, Fromm M, Blasig IE, Huber O (2013) CK2-dependent phosphorylation of occludin regulates the interaction with ZO-proteins and tight junction integrity. Cell Commun Signal 11(1):40.  https://doi.org/10.1186/1478-811X-11-40 Google Scholar
  74. 74.
    Tscheik C, Blasig IE, Winkler L (2013) Trends in drug delivery through tissue barriers containing tight junctions. Tissue Barriers 1(2):e24565.  https://doi.org/10.4161/tisb.24565 Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Philipp Berndt
    • 1
  • Lars Winkler
    • 1
    Email author
  • Jimmi Cording
    • 1
  • Olga Breitkreuz-Korff
    • 1
  • André Rex
    • 2
  • Sophie Dithmer
    • 1
  • Valentina Rausch
    • 1
  • Rosel Blasig
    • 1
  • Matthias Richter
    • 3
  • Anje Sporbert
    • 3
  • Hartwig Wolburg
    • 4
  • Ingolf E. Blasig
    • 1
  • Reiner F. Haseloff
    • 1
    Email author
  1. 1.Leibniz-Forschungsinstitut für Molekulare PharmakologieBerlinGermany
  2. 2.Department of Experimental NeurologyCharité-Universitätsmedizin BerlinBerlinGermany
  3. 3.Max-Delbrück-Centrum für Molekulare MedizinBerlinGermany
  4. 4.Institut für Pathologie und NeuropathologieUniversität TübingenTübingenGermany

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