Endothelial tight junctions: permeable barriers of the vessel wall

Gianfranco Bazzoni

doi:10.1160/TH05-07-0488

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 95(01): 36-42
DOI: 10.1160/TH05-07-0488

Theme Issue Article

Schattauer GmbH

Endothelial tight junctions: permeable barriers of the vessel wall

Gianfranco Bazzoni

¹Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy

› Author Affiliations

Abstract

Summary

The endothelial lining of the vessel wall is a permeable barrier, which is located at the interface between the vascular and the perivascular compartments. Although the endothelium acts as an efficient barrier that strictly separates the two compartments,it may also act as a permeable filter which allows selective exchange of solutes and water between the luminal and abluminal sides of the barrier. Similarly to epithelia, also in the endothelium permeability follows two distinct routes, which have been termed transcellular pathway (across the apical and basolateral membranes of individual cells) and paracellular pathway (through the intercellular junctions and the lateral spaces between contacting cells). After an initial description of the two pathways, the review focuses on the cellular and molecular basis of the paracellular pathway, with emphasis on the role of intercellular tight junctions and tight junction-associated claudins. Finally, the signaling events that regulate paracellular permeability are discussed.

Keywords

Endothelial cells - permeability - tight junctions - ion channels

Full Text

References

References
1 Yu AS. Claudins and epithelial paracellular transport: the end of the beginning. Curr Opin Nephrol Hypertens 2003; 12: 503-9.
2 Van Itallie CM, Anderson JM. The molecular physiology of tight junction pores. Physiology (Bethesda) 2004; 19: 331-8.
3 Powell DW. Barrier function of epithelia. AmJ Physiol 1981; 241: G275-88.
4 Mann GE, Yudilevich DL, Sobrevia L. Regulation of amino acid and glucose transporters in endothelial and smooth muscle cells. Physiol Rev 2003; 83: 183-252.
5 Nilius B, Droogmans G. Ion channels and their functional role in vascular endothelium. Physiol Rev 2001; 81: 1415-59.
6 Predescu D, Vogel SM, Malik AB. Functional and morphological studies of protein transcytosis in continuous endothelia. Am J Physiol Lung Cell Mol Physiol 2004; 287: L895-901.
7 Pappenheimer JR, Reiss KZ. Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat. J Membr Biol 1987; 100: 123-36.
8 Hecht G, Pestic L, Nikcevic G. et al. Expression of the catalytic domain of myosin light chain kinase increases paracellular permeability. Am J Physiol 1996; 271: C1678-84.
9 Turner JR, Rill BK, Carlson SL. et al. Physiological regulation of epithelial tight junctions is associated with myosin light-chain phosphorylation. Am J Physiol 1997; 273: C1378-85.
10 Ghitescu L, Fixman A, Simionescu M. et al. Specific binding sites for albumin restricted to plasmalemmal vesicles of continuous capillary endothelium: receptor-mediated transcytosis. J Cell Biol 1986; 102: 1304-11.
11 Schnitzer JE, Carley WW, Palade GE. Albumin interacts specifically with a 60-kDa microvascular endothelial glycoprotein. Proc Natl Acad Sci USA 1988; 85: 6773-7.
12 Farquhar MG, Palade GE. Junctional complexes in various epithelia. J Cell Biol 1963; 17: 375-412.
13 Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2001; 02: 285-93.
14 D’Atri F, Citi S. Molecular complexity of vertebrate tight junctions (Review). Mol Membr Biol 2002; 19: 103-12.
15 Matter K, Balda MS. Signalling to and from tight junctions. Nat Rev Mol Cell Biol 2003; 04: 225-36.
16 Schneeberger EE, Lynch RD. The tight junction: a multifunctional complex. Am J Physiol Cell Physiol 2004; 286: C1213-28.
17 Bazzoni G. The JAM family of junctional adhesion molecules. Curr Opin Cell Biol 2003; 15: 525-30.
18 Bazzoni G, Dejana E. Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev 2004; 84: 869-901.
19 Furuse M, Hirase T, Itoh M. et al. Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 1993; 123: 1777-88.
20 Van Itallie CM, Anderson JM. Occludin confers adhesiveness when expressed in fibroblasts. J Cell Sci 1997; 110: 1113-21.
21 Wong V, Gumbiner BM. A synthetic peptide corresponding to the extracellular domain of occludin perturbs the tight junction permeability barrier. J Cell Biol 1997; 136: 399-409.
22 Balda MS, Whitney JA, Flores C. et al. 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 1996; 134: 1031-49.
23 Hirase T, Staddon JM, Saitou M. et al. Occludin asa possible determinant of tight junction permeability in endothelial cells. J Cell Sci 1997; 110: 1603-13.
24 Furuse M, Sasaki H, Fujimoto K. et al. A single gene product, claudin-1 or -2, reconstitutes tight junction strands and recruits occludin in fibroblasts. J Cell Biol 1998; 143: 391-401.
25 Kostrewa D, Brockhaus M, D’Arcy A. et al. X-ray structure of junctional adhesion molecule: structural basis for homophilic adhesion viaa novel dimerization motif. EmboJ 2001; 20: 4391-8.
26 Prota AE, Campbell JA, Schelling P. et al. Crystal structure of human junctional adhesion molecule 1: implications for reovirus binding. Proc Natl Acad Sci USA 2003; 100: 5366-71.
27 Bazzoni G, Martinez-Estrada OM, Mueller F. et al. Homophilic interaction of junctional adhesion molecule. J Biol Chem 2000; 275: 30970-6.
28 Martin-Padura I, Lostaglio S, Schneemann M. et al. Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. J Cell Biol 1998; 142: 117-27.
29 Liang TW, DeMarco RA, Mrsny RJ. et al. Characterization of huJAM: evidence for involvement in cell-cell contact and tight junction regulation. Am J Physiol Cell Physiol 2000; 279: C1733-43.
30 Liu Y, Nusrat A, Schnell FJ. et al. Human junction adhesion molecule regulates tight junction resealing in epithelia. J Cell Sci 2000; 113: 2363-74.
31 Mandell KJ, Parkos CA. The JAM family of proteins. Adv Drug Deliv Rev 2005; 57: 857-67.
32 Aurrand-Lions M, Johnson-Leger C, Wong C. et al. Heterogeneity of endothelial junctions is reflected by differential expression and specific subcellular localization of the three JAM family members. Blood 2001; 98: 3699-707.
33 Furuse M, Furuse K, Sasaki H. et al. Conversion of zonulae occludentes from tight to leaky strand type by introducing claudin-2 into Madin-Darby canine kidney I cells. J Cell Biol 2001; 153: 263-72.
34 Amasheh S, Meiri N, Gitter AH. et al. Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells. J Cell Sci 2002; 115: 4969-76.
35 Tsukita S, Furuse M. Pores in the wall: claudins constitute tight junction strands containing aqueous pores. J Cell Biol 2000; 149: 13-6.
36 McCarthy KM, Francis SA, McCormack JM. et al. Inducible expression of claudin-1-myc but not occludin-VSV-G results in aberrant tight junction strand formation in MDCK cells. J Cell Sci 2000; 113: 3387-98.
37 Van Itallie C, Rahner C, Anderson JM. Regulated expression of claudin-4 decreases paracellular conductance through a selective decrease in sodium permeability. J Clin Invest 2001; 107: 1319-27.
38 Yu AS, Enck AH, Lencer WI. et al. Claudin-8 expression in Madin-Darby canine kidney cells augments the paracellular barrier to cation permeation. J Biol Chem 2003; 278: 17350-9.
39 Colegio OR, Van Itallie CM, McCrea HJ. et al. Claudins create charge-selective channels in the paracellular pathway between epithelial cells. AmJ Physiol Cell Physiol 2002; 283: C142-7.
40 Claude P, Goodenough DA. Fracture faces of zonulae occludentes from „tight” and „leaky” epithelia. J Cell Biol 1973; 58: 390-400.
41 Furuse M, Sasaki H, Tsukita S. Manner of interaction of heterogeneous claudin species within and between tight junction strands. J Cell Biol 1999; 147: 891-903.
42 Nitta T, Hata M, Gotoh S. et al. Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J Cell Biol 2003; 161: 653-60.
43 Yuan SY. Protein kinase signaling in the modulation of microvascular permeability. Vascul Pharmacol 2002; 39: 213-23.
44 Krizbai IA, Deli MA. Signalling pathways regulating the tight junction permeability in the blood-brain barrier. Cell Mol Biol (Noisy-le-grand) 2003; 49: 23-31.
45 Balda MS, Gonzalez-Mariscal L, Matter K. et al. Assembly of the tight junction: the role of diacylglycerol. J Cell Biol 1993; 123: 293-302.
46 Andreeva AY, Krause E, Muller EC. et al. Protein kinase C regulates the phosphorylation and cellular localization of occludin. J Biol Chem 2001; 276: 38480-6.
47 Stuart RO, Nigam SK. Regulated assembly of tight junctions by protein kinase C. Proc Natl Acad Sci USA 1995; 92: 6072-6.
48 Wolburg H, Neuhaus J, Kniesel U. et al. Modulation of tight junction structure in blood-brain barrier endothelial cells Effects of tissue culture, second messengers and cocultured astrocytes. J Cell Sci 1994; 107: 1347-57.
49 Mullin JM, Kampherstein JA, Laughlin KV. et al. Overexpression of protein kinase C-delta increases tight junction permeability in LLC-PK1 epithelia. AmJ Physiol 1998; 275: C544-54.
50 Citi S. Protein kinase inhibitors prevent junction dissociation induced by low extracellular calcium in MDCK epithelial cells. J Cell Biol 1992; 117: 169-78.
51 Hecht G, Robinson B, Koutsouris A. Reversible disassembly of an intestinal epithelial monolayer by prolonged exposure to phorbol ester. Am J Physiol 1994; 266: G214-21.
52 Turner JR, Angle JM, Black ED. et al. PKC-dependent regulation of transepithelial resistance: roles of MLC and MLC kinase. Am J Physiol 1999; 277: C554-62.
53 Suzuki A, Yamanaka T, Hirose T. et al. Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures. J Cell Biol 2001; 152: 1183-96.
54 Cereijido M, Contreras RG, Shoshani L. Cell adhesion, polarity, and epithelia in the dawn of metazoans. Physiol Rev 2004; 84: 1229-62.
55 Meyer TN, Schwesinger C, Ye J. et al. Reassembly of the tight junction after oxidative stress depends on tyrosine kinase activity. J Biol Chem 2001; 276: 22048-55.
56 Chen YH, Lu Q, Goodenough DA. et al. Nonreceptor tyrosine kinase c-Yes interacts with occludin during tight junction formation in canine kidney epithelial cells. Mol Biol Cell 2002; 13: 1227-37.
57 Staddon JM, Herrenknecht K, Smales C. et al. Evidence that tyrosine phosphorylation may increase tight junction permeability. J Cell Sci 1995; 108: 609-19.
58 Kevil CG, Oshima T, Alexander B. et al. H(2)O(2)mediated permeability: role of MAPK and occludin. Am J Physiol Cell Physiol 2000; 279: C21-30.
59 Saha C, Nigam SK, Denker BM. Expanding role of G proteins in tight junction regulation: Galpha(s) stimulates TJ assembly. Biochem Biophys Res Commun 2001; 285: 250-6.
60 Meyer TN, Schwesinger C, Denker BM. Zonula occludens-1 is a scaffolding protein for signaling molecules Galpha(12) directly binds to the Src homology 3 domain and regulates paracellular permeability in epithelial cells. J Biol Chem 2002; 277: 24855-8.
61 Denker BM, Saha C, Khawaja S. et al. Involvement of a heterotrimeric G protein alpha subunit in tight junction biogenesis. J Biol Chem 1996; 271: 25750-3.
62 Rist RJ, Romero IA, Chan MW. et al. F-actin cytoskeleton and sucrose permeability of immortalised rat brain microvascular endothelial cell monolayers: effects of cyclic AMP and astrocytic factors. Brain Res 1997; 768: 10-8.
63 Hurst RD, Clark JB. Alterations in transendothelial electrical resistance by vasoactive agonists and cyclic AMP in a blood-brain barrier model system. Neurochem Res 1998; 23: 149-54.
64 Rubin LL, Hall DE, Porter S. et al. A cell culture model of the blood-brain barrier. J Cell Biol 1991; 115: 1725-35.
65 Mayhan WG. VEGF increases permeability of the blood-brain barrier via a nitric oxide synthase/cGMPdependent pathway. Am J Physiol 1999; 276: C1148-53.
66 Sporbert A, Mertsch K, Smolenski A. et al. Phosphorylation of vasodilator-stimulated phosphoprotein: a consequence of nitric oxideand cGMP-mediated signal transduction in brain capillary endothelial cells and astrocytes. Brain Res Mol Brain Res 1999; 67: 258-66.
67 Nusrat A, Giry M, Turner JR. et al. Rho protein regulates tight junctions and perijunctional actin organization in polarized epithelia. Proc Natl Acad Sci USA 1995; 92: 10629-33.
68 Jou TS, Schneeberger EE, Nelson WJ. Structural and functional regulation of tight junctions by RhoA and Rac1 small GTPases. J Cell Biol 1998; 142: 101-15.
69 Benais-Pont G, Punn A, Flores-Maldonado C. et al. Identification of a tight junction-associated guanine nucleotide exchange factor that activates Rho and regulates paracellular permeability. J Cell Biol 2003; 160: 729-40.
70 Fujita H, Katoh H, Hasegawa H. et al. Molecular decipherment of Rho effector pathways regulating tight-junction permeability. Biochem J 2000; 346: 617-22.
71 Hirase T, Kawashima S, Wong EY. et al. Regulation of tight junction permeability and occludin phosphorylation by Rhoa-p160ROCK-dependent and -independent mechanisms. J Biol Chem 2001; 276: 10423-31.
72 Furuse M, Itoh M, Hirase T. et al. Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions. J Cell Biol 1994; 127: 1617-26.
73 Itoh M, Furuse M, Morita K. et al. Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. J Cell Biol 1999; 147: 1351-63.
74 Bazzoni G, Martinez-Estrada OM, Orsenigo F. et al. Interaction of junctional adhesion molecule with the tight junction components ZO-1, cingulin, and occludin. J Biol Chem 2000; 275: 20520-6.
75 Ebnet K, Schulz CU, Meyer Zu, Brickwedde MK. et al. Junctional adhesion molecule interacts with the PDZ domain-containing proteins AF-6 and ZO-1. J Biol Chem 2000; 275: 27979-88.
76 Fanning AS, Jameson BJ, Jesaitis LA. et al. The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton. J Biol Chem 1998; 273: 29745-53.
77 Itoh M, Nagafuchi A, Moroi S. et al. Involvement of ZO-1 in cadherin-based cell adhesion through its direct binding to alpha catenin and actin filaments. J Cell Biol 1997; 138: 181-92.
78 Katsube T, Takahisa M, Ueda R. et al. Cortactin associates with the cell-cell junction protein ZO-1 in both Drosophila and mouse. J Biol Chem 1998; 273: 29672-7.
79 Cordenonsi M, D’Atri F, Hammar E. et al. Cingulin contains globular and coiled-coil domains and interacts with ZO-1, ZO-2, ZO-3, and myosin. J Cell Biol 1999; 147: 1569-82.
80 Martinez-Estrada OM, Villa A, Breviario F. et al. Association of junctional adhesion molecule with calcium/calmodulin-dependent serine protein kinase (CASK/LIN-2) in human epithelial caco-2 cells. J Biol Chem 2001; 276: 9291-6.
81 Bruewer M, Luegering A, Kucharzik T. et al. Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms. J Immunol 2003; 171: 6164-72.
82 Martinez-Estrada OM, Manzi L, Tonetti P. et al. Opposite effects of tumor necrosis factor and soluble fibronectin on junctional adhesion molecule-A in endothelial cells. Am J Physiol Lung Cell Mol Physiol 2005; 288: L1081-8.
83 Ebnet K, Suzuki A, Horikoshi Y. et al. The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM). Embo J 2001; 20: 3738-48.
84 Itoh M, Sasaki H, Furuse M. et al. Junctional adhesion molecule (JAM) binds to PAR-3: a possible mechanism for the recruitment of PAR-3 to tight junctions. J Cell Biol 2001; 154: 491-7.
85 Hardin J, Lockwood C. Skin tight: cell adhesion in the epidermis of Caenorhabditis elegans. Curr Opin Cell Biol 2004; 16: 486-92.
86 Jane SM, Ting SB, Cunningham JM. Epidermal impermeable barriers in mouse and fly. Curr Opin Genet Dev 2005; 15: 447-53.