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Tight junction dynamics: the role of junctional adhesion molecules (JAMs)

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Abstract

Junctional adhesion molecules (JAMs) are a family of adhesion molecules localized at the tight junction of polarized cells and on the cell surface of leukocytes. The last 20 years of research in this field has shown that several members of the family play an important role in the regulation of cell polarity, endothelium permeability and leukocytes migration. They mediate these pleiotropic functions through a multitude of homophilic and heterophilic interactions with intrafamily and extrafamily partners. In this article, we review the current status of the JAM family and highlight their functional role in tight junction dynamics and leukocyte transmigration.

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References

  • Angelow S, Ahlstrom R, Yu AS (2008) Biology of claudins. Am J Physiol Ren Physiol 295:F867–F876

    CAS  Google Scholar 

  • Arrate MP, Rodriguez JM, Tran TM, Brock TA, Cunningham SA (2001) Cloning of human junctional adhesion molecule 3 (JAM3) and its identification as the JAM2 counter-receptor. J Biol Chem 276:45826–45832

    PubMed  CAS  Google Scholar 

  • Arthur FE, Shivers RR, Bowman PD (1987) Astrocyte-mediated induction of tight junctions in brain capillary endothelium: an efficient in vitro model. Brain Res 433:155–159

    PubMed  CAS  Google Scholar 

  • Asakura T, Nakanishi H, Sakisaka T, Takahashi K, Mandai K, Nishimura M, Sasaki T, Takai Y (1999) Similar and differential behaviour between the nectin-afadin-ponsin and cadherin-catenin systems during the formation and disruption of the polarized junctional alignment in epithelial cells. Genes Cells 4:573–581

    PubMed  CAS  Google Scholar 

  • Aurrand-Lions MA, Duncan L, Pasquier LD, Imhof BA (2000) Cloning of JAM-2 and JAM-3: an emerging junctional adhesion molecular family? Curr Top Microbiol Immunol 251:91–98

    PubMed  CAS  Google Scholar 

  • Aurrand-Lions M, Duncan L, Ballestrem C, Imhof BA (2001a) JAM-2, a novel immunoglobulin superfamily molecule, expressed by endothelial and lymphatic cells. J Biol Chem 276:2733–2741

    PubMed  CAS  Google Scholar 

  • Aurrand-Lions M, Johnson-Leger C, Wong C, Pasquier LD, Imhof BA (2001b) Heterogeneity of endothelial junctions is reflected by differential expression and specific subcellular localization of the three JAM family members. Blood 98:3699–3707

    PubMed  CAS  Google Scholar 

  • Barton ES, Forrest JC, Connolly JL, Chappell JD, Liu Y, Schnell FJ, Nusrat A, Parkos CA, Dermody TS (2001) Junction adhesion molecule is a receptor for reovirus. Cell 104:441–451

    PubMed  CAS  Google Scholar 

  • Bazzoni G, Dejana E (2004) Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev 84:869–901

    PubMed  CAS  Google Scholar 

  • Bazzoni G, Martinez-Estrada OM, Mueller F, Nelboeck P, Schmid G, Bartfai T, Dejana E, Brockhaus M (2000) Homophilic interaction of junctional adhesion molecule. J Biol Chem 275:30970–30976

    PubMed  CAS  Google Scholar 

  • Bergelson JM, Cunningham JA, Droguett G, Kurt-Jones EA, Krithivas A, Hong JS, Horwitz MS, Crowell RL, Finberg RW (1997) Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 275:1320–1323

    PubMed  CAS  Google Scholar 

  • Bradfield PF, Nourshargh S, Aurrand-Lions M, Imhof BA (2007a) JAM family and related proteins in leukocyte migration (Vestweber series). Arterioscler Thromb Vasc Biol 27:2104–2112

    PubMed  CAS  Google Scholar 

  • Bradfield PF, Scheiermann C, Nourshargh S, Ody C, Luscinskas FW, Rainger GE, Nash GB, Miljkovic-Licina M, Aurrand-Lions M, Imhof BA (2007b) JAM-C regulates unidirectional monocyte transendothelial migration in inflammation. Blood 110:2545–2555

    PubMed Central  PubMed  CAS  Google Scholar 

  • Brightman MW, Reese TS (1969) Junctions between intimately apposed cell membranes in the vertebrate brain. J Cell Biol 40:648–677

    PubMed Central  PubMed  CAS  Google Scholar 

  • Butcher EC, Picker LJ (1996) Lymphocyte homing and homeostasis. Science 272:60–66

    PubMed  CAS  Google Scholar 

  • Cera MR, Del Prete A, Vecchi A, Corada M, Martin-Padura I, Motoike T, Tonetti P, Bazzoni G, Vermi W, Gentili F, Bernasconi S, Sato TN, Mantovani A, Dejana E (2004) Increased DC trafficking to lymph nodes and contact hypersensitivity in junctional adhesion molecule-A-deficient mice. J Clin Invest 114:729–738

    PubMed Central  PubMed  CAS  Google Scholar 

  • Chretien I, Marcuz A, Courtet M, Katevuo K, Vainio O, Heath JK, White SJ, Pasquier LD (1998) CTX, a Xenopus thymocyte receptor, defines a molecular family conserved throughout vertebrates. Eur J Immunol 28:4094–4104

    PubMed  CAS  Google Scholar 

  • Christen S, Coppieters K, Rose K, Holdener M, Bayer M, Pfeilschifter JM, Hintermann E, von Herrath MG, Aurrand-Lions M, Imhof BA, Christen U (2013) Blockade but not overexpression of the junctional adhesion molecule C influences virus-induced type 1 diabetes in mice. PLoS ONE 8:e54675

    PubMed Central  PubMed  CAS  Google Scholar 

  • Claude P (1978) Morphological factors influencing transepithelial permeability: a model for the resistance of the zonula occludens. J Membr Biol 39:219–232

    PubMed  CAS  Google Scholar 

  • Claude P, Goodenough DA (1973) Fracture faces of zonulae occludentes from "tight" and "leaky" epithelia. J Cell Biol 58:390–400

    PubMed Central  PubMed  CAS  Google Scholar 

  • Cohen CJ, Shieh JT, Pickles RJ, Okegawa T, Hsieh JT, Bergelson JM (2001) The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction. Proc Natl Acad Sci U S A 98:15191–15196

    PubMed Central  PubMed  CAS  Google Scholar 

  • Coyne CB, Voelker T, Pichla SL, Bergelson JM (2004) The coxsackievirus and adenovirus receptor interacts with the multi-PDZ domain protein-1 (MUPP-1) within the tight junction. J Biol Chem 279:48079–48084

    PubMed  CAS  Google Scholar 

  • Cunningham SA, Arrate MP, Rodriguez JM, Bjercke RJ, Vanderslice P, Morris AP, Brock TA (2000) A novel protein with homology to the junctional adhesion molecule. Characterization of leukocyte interactions. J Biol Chem 275:34750–34756

    PubMed  CAS  Google Scholar 

  • Cunningham SA, Rodriguez JM, Arrate MP, Tran TM, Brock TA (2002) JAM2 interacts with alpha4beta1. Facilitation by JAM3. J Biol Chem 277:27589–27592

    PubMed  CAS  Google Scholar 

  • Del Maschio A, De Luigi A, Martin-Padura I, Brockhaus M, Bartfai T, Fruscella P, Adorini L, Martino G, Furlan R, De Simoni MG, Dejana E (1999) Leukocyte recruitment in the cerebrospinal fluid of mice with experimental meningitis is inhibited by an antibody to junctional adhesion molecule (JAM). J Exp Med 190:1351–1356

    PubMed Central  PubMed  Google Scholar 

  • Du Pasquier L, Courtet M, Chretien I (1999) Duplication and MHC linkage of the CTX family of genes in Xenopus and in mammals. Eur J Immunol 29:1729–1739

    PubMed  Google Scholar 

  • Ebnet K, Schulz CU, Meyer Zu Brickwedde MK, Pendl GG, Vestweber D (2000) Junctional adhesion molecule interacts with the PDZ domain-containing proteins AF-6 and ZO-1. J Biol Chem 275:27979–27988

    PubMed  CAS  Google Scholar 

  • Ebnet K, Suzuki A, Horikoshi Y, Hirose T, Meyer Zu Brickwedde MK, Ohno S, Vestweber D (2001) The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM). EMBO J 20:3738–3748

    PubMed Central  PubMed  CAS  Google Scholar 

  • Ebnet K, Aurrand-Lions M, Kuhn A, Kiefer F, Butz S, Zander K, Meyer zu Brickwedde MK, Suzuki A, Imhof BA, Vestweber D (2003) The junctional adhesion molecule (JAM) family members JAM-2 and JAM-3 associate with the cell polarity protein PAR-3: a possible role for JAMs in endothelial cell polarity. J Cell Sci 116:3879–3891

    PubMed  CAS  Google Scholar 

  • Engelhardt B, Ransohoff RM (2012) Capture, crawl, cross: the T cell code to breach the blood–brain barriers. Trends Immunol 33:579–589

    PubMed  CAS  Google Scholar 

  • Excoffon KJ, Hruska-Hageman A, Klotz M, Traver GL, Zabner J (2004) A role for the PDZ-binding domain of the coxsackie B virus and adenovirus receptor (CAR) in cell adhesion and growth. J Cell Sci 117:4401–4409

    PubMed  CAS  Google Scholar 

  • Fanning AS, Jameson BJ, Jesaitis LA, Anderson JM (1998) The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton. J Biol Chem 273:29745–29753

    PubMed  CAS  Google Scholar 

  • Farquhar MG, Palade GE (1963) Junctional complexes in various epithelia. J Cell Biol 17:375–412

    PubMed Central  PubMed  CAS  Google Scholar 

  • Fechner H, Haack A, Wang H, Wang X, Eizema K, Pauschinger M, Schoemaker R, Veghel R, Houtsmuller A, Schultheiss HP, Lamers J, Poller W (1999) Expression of coxsackie adenovirus receptor and alphav-integrin does not correlate with adenovector targeting in vivo indicating anatomical vector barriers. Gene Ther 6:1520–1535

    PubMed  CAS  Google Scholar 

  • Fukuhara A, Irie K, Yamada A, Katata T, Honda T, Shimizu K, Nakanishi H, Takai Y (2002) Role of nectin in organization of tight junctions in epithelial cells. Genes Cells 7:1059–1072

    PubMed  CAS  Google Scholar 

  • Furuse M, Tsukita S (2006) Claudins in occluding junctions of humans and flies. Trends Cell Biol 16:181–188

    PubMed  CAS  Google Scholar 

  • 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 143:391–401

    PubMed Central  PubMed  CAS  Google Scholar 

  • Gao L, Macara IG, Joberty G (2002) Multiple splice variants of Par3 and of a novel related gene, Par3L, produce proteins with different binding properties. Gene 294:99–107

    PubMed  CAS  Google Scholar 

  • Garrido-Urbani S, Bradfield PF, Lee BP, Imhof BA (2008) Vascular and epithelial junctions: a barrier for leucocyte migration. Biochem Soc Trans 36:203–211

    PubMed  CAS  Google Scholar 

  • Gliki G, Ebnet K, Aurrand-Lions M, Imhof BA, Adams RH (2004) Spermatid differentiation requires the assembly of a cell polarity complex downstream of junctional adhesion molecule-C. Nature 431:320–324

    PubMed  CAS  Google Scholar 

  • Guillemot L, Paschoud S, Pulimeno P, Foglia A, Citi S (2008) The cytoplasmic plaque of tight junctions: a scaffolding and signalling center. Biochim Biophys Acta 1778:601–613

    PubMed  CAS  Google Scholar 

  • Guo YL, Bai R, Chen CX, Liu DQ, Liu Y, Zhang CY, Zen K (2009) Role of junctional adhesion molecule-like protein in mediating monocyte transendothelial migration. Arterioscler Thromb Vasc Biol 29:75–83

    PubMed  Google Scholar 

  • Hamazaki Y, Itoh M, Sasaki H, Furuse M, Tsukita S (2002) Multi-PDZ domain protein 1 (MUPP1) is concentrated at tight junctions through its possible interaction with claudin-1 and junctional adhesion molecule. J Biol Chem 277:455–461

    PubMed  CAS  Google Scholar 

  • Hirabayashi S, Tajima M, Yao I, Nishimura W, Mori H, Hata Y (2003) JAM4, a junctional cell adhesion molecule interacting with a tight junction protein, MAGI-1. Mol Cell Biol 23:4267–4282

    PubMed Central  PubMed  CAS  Google Scholar 

  • Hirata K, Ishida T, Penta K, Rezaee M, Yang E, Wohlgemuth J, Quertermous T (2001) Cloning of an immunoglobulin family adhesion molecule selectively expressed by endothelial cells. J Biol Chem 276:16223–16231

    CAS  Google Scholar 

  • Iden S, Misselwitz S, Peddibhotla SS, Tuncay H, Rehder D, Gerke V, Robenek H, Suzuki A, Ebnet K (2012) aPKC phosphorylates JAM-A at Ser285 to promote cell contact maturation and tight junction formation. J Cell Biol 196:623–639

    PubMed Central  PubMed  CAS  Google Scholar 

  • Inoue M, Ishida T, Yasuda T, Toh R, Hara T, Cangara HM, Rikitake Y, Taira K, Sun L, Kundu RK, Quertermous T, Hirata K (2010) Endothelial cell-selective adhesion molecule modulates atherosclerosis through plaque angiogenesis and monocyte-endothelial interaction. Microvasc Res 80:179–187

    PubMed  CAS  Google Scholar 

  • Itoh M, Sasaki H, Furuse M, Ozaki H, Kita T, Tsukita S (2001) Junctional adhesion molecule (JAM) binds to PAR-3: a possible mechanism for the recruitment of PAR-3 to tight junctions. J Cell Biol 154:491–497

    PubMed Central  PubMed  CAS  Google Scholar 

  • Johnson-Leger C, Imhof BA (2003) Forging the endothelium during inflammation: pushing at a half-open door? Cell Tissue Res 314:93–105

    PubMed  CAS  Google Scholar 

  • Johnson-Leger CA, Aurrand-Lions M, Beltraminelli N, Fasel N, Imhof BA (2002) Junctional adhesion molecule-2 (JAM-2) promotes lymphocyte transendothelial migration. Blood 100:2479–2486

    PubMed  CAS  Google Scholar 

  • Kansaku A, Hirabayashi S, Mori H, Fujiwara N, Kawata A, Ikeda M, Rokukawa C, Kurihara H, Hata Y (2006) Ligand-of-Numb protein X is an endocytic scaffold for junctional adhesion molecule 4. Oncogene 25:5071–5084

    PubMed  CAS  Google Scholar 

  • Keiper T, Al-Fakhri N, Chavakis E, Athanasopoulos AN, Isermann B, Herzog S, Saffrich R, Hersemeyer K, Bohle RM, Haendeler J, Preissner KT, Santoso S, Chavakis T (2005) The role of junctional adhesion molecule-C (JAM-C) in oxidized LDL-mediated leukocyte recruitment. FASEB J 19:2078–2080

    PubMed  CAS  Google Scholar 

  • Khounlotham M, Kim W, Peatman E, Nava P, Medina-Contreras O, Addis C, Koch S, Fournier B, Nusrat A, Denning TL, Parkos CA (2012) Compromised intestinal epithelial barrier induces adaptive immune compensation that protects from colitis. Immunity 37:563–573

    PubMed Central  PubMed  CAS  Google Scholar 

  • Koenen RR, Pruessmeyer J, Soehnlein O, Fraemohs L, Zernecke A, Schwarz N, Reiss K, Sarabi A, Lindbom L, Hackeng TM, Weber C, Ludwig A (2009) Regulated release and functional modulation of junctional adhesion molecule A by disintegrin metalloproteinases. Blood 113:4799–4809

    PubMed  CAS  Google Scholar 

  • Kostrewa D, Brockhaus M, D'Arcy A, Dale GE, Nelboeck P, Schmid G, Mueller F, Bazzoni G, Dejana E, Bartfai T, Winkler FK, Hennig M (2001) X-ray structure of junctional adhesion molecule: structural basis for homophilic adhesion via a novel dimerization motif. EMBO J 20:4391–4398

    PubMed Central  PubMed  CAS  Google Scholar 

  • Lakshmi SP, Reddy AT, Naik MU, Naik UP, Reddy RC (2012) Effects of JAM-A deficiency or blocking antibodies on neutrophil migration and lung injury in a murine model of ALI. Am J Physiol Lung Cell Mol Physiol 303:L758–L766

    PubMed Central  PubMed  CAS  Google Scholar 

  • Lamagna C, Meda P, Mandicourt G, Brown J, Gilbert RJ, Jones EY, Kiefer F, Ruga P, Imhof BA, Aurrand-Lions M (2005) Dual interaction of JAM-C with JAM-B and alpha(M)beta2 integrin: function in junctional complexes and leukocyte adhesion. Mol Biol Cell 16:4992–5003

    PubMed Central  PubMed  CAS  Google Scholar 

  • Laukoetter MG, Nava P, Lee WY, Severson EA, Capaldo CT, Babbin BA, Williams IR, Koval M, Peatman E, Campbell JA, Dermody TS, Nusrat A, Parkos CA (2007) JAM-A regulates permeability and inflammation in the intestine in vivo. J Exp Med 204:3067–3076

    PubMed Central  PubMed  CAS  Google Scholar 

  • Lechner F, Sahrbacher U, Suter T, Frei K, Brockhaus M, Koedel U, Fontana A (2000) Antibodies to the junctional adhesion molecule cause disruption of endothelial cells and do not prevent leukocyte influx into the meninges after viral or bacterial infection. J Infect Dis 182:978–982

    PubMed  CAS  Google Scholar 

  • Li X, Stankovic M, Lee BP, Aurrand-Lions M, Hahn CN, Lu Y, Imhof BA, Vadas MA, Gamble JR (2009) JAM-C induces endothelial cell permeability through its association and regulation of {beta}3 integrins. Arterioscler Thromb Vasc Biol 29:1200–1206

    PubMed  CAS  Google Scholar 

  • Liang TW, DeMarco RA, Mrsny RJ, Gurney A, Gray A, Hooley J, Aaron HL, Huang A, Klassen T, Tumas DB, Fong S (2000) Characterization of huJAM: evidence for involvement in cell-cell contact and tight junction regulation. Am J Physiol Cell Physiol 279:C1733–C1743

    PubMed  CAS  Google Scholar 

  • Liang TW, Chiu HH, Gurney A, Sidle A, Tumas DB, Schow P, Foster J, Klassen T, Dennis K, DeMarco RA, Pham T, Frantz G, Fong S (2002) Vascular endothelial-junctional adhesion molecule (VE-JAM)/JAM 2 interacts with T, NK, and dendritic cells through JAM 3. J Immunol 168:1618–1626

    PubMed  CAS  Google Scholar 

  • Liu Y, Nusrat A, Schnell FJ, Reaves TA, Walsh S, Pochet M, Parkos CA (2000) Human junction adhesion molecule regulates tight junction resealing in epithelia. J Cell Sci 113(Pt 13):2363–2374

    PubMed  CAS  Google Scholar 

  • Ludwig RJ, Zollner TM, Santoso S, Hardt K, Gille J, Baatz H, Johann PS, Pfeffer J, Radeke HH, Schon MP, Kaufmann R, Boehncke WH, Podda M (2005) Junctional adhesion molecules (JAM)-B and -C contribute to leukocyte extravasation to the skin and mediate cutaneous inflammation. J Investig Dermatol 125:969–976

    PubMed  CAS  Google Scholar 

  • Ludwig RJ, Hardt K, Hatting M, Bistrian R, Diehl S, Radeke HH, Podda M, Schon MP, Kaufmann R, Henschler R, Pfeilschifter JM, Santoso S, Boehncke WH (2009) Junctional adhesion molecule (JAM)-B supports lymphocyte rolling and adhesion through interaction with alpha4beta1 integrin. Immunology 128:196–205

    PubMed Central  PubMed  CAS  Google Scholar 

  • Luissint AC, Lutz PG, Calderwood DA, Couraud PO, Bourdoulous S (2008) JAM-L-mediated leukocyte adhesion to endothelial cells is regulated in cis by alpha4beta1 integrin activation. J Cell Biol 183:1159–1173

    PubMed Central  PubMed  CAS  Google Scholar 

  • Mamdouh Z, Mikhailov A, Muller WA (2009) Transcellular migration of leukocytes is mediated by the endothelial lateral border recycling compartment. J Exp Med 206:2795–2808

    PubMed Central  PubMed  CAS  Google Scholar 

  • Mandell KJ, Parkos CA (2005) The JAM family of proteins. Adv Drug Deliv Rev 57:857–867

    PubMed  CAS  Google Scholar 

  • Mandell KJ, Babbin BA, Nusrat A, Parkos CA (2005) Junctional adhesion molecule 1 regulates epithelial cell morphology through effects on beta1 integrins and Rap1 activity. J Biol Chem 280:11665–11674

    PubMed  CAS  Google Scholar 

  • Mandell KJ, Holley GP, Parkos CA, Edelhauser HF (2006) Antibody blockade of junctional adhesion molecule-A in rabbit corneal endothelial tight junctions produces corneal swelling. Investig Ophthalmol Vis Sci 47:2408–2416

    Google Scholar 

  • Mandicourt G, Iden S, Ebnet K, Aurrand-Lions M, Imhof BA (2007) JAM-C regulates tight junctions and integrin-mediated cell adhesion and migration. J Biol Chem 282:1830–1837

    PubMed  CAS  Google Scholar 

  • Mapoles JE, Krah DL, Crowell RL (1985) Purification of a HeLa cell receptor protein for group B coxsackieviruses. J Virol 55:560–566

    PubMed Central  PubMed  CAS  Google Scholar 

  • Martinez-Estrada OM, Villa A, Breviario F, Orsenigo F, Dejana E, Bazzoni G (2001) Association of junctional adhesion molecule with calcium/calmodulin-dependent serine protein kinase (CASK/LIN-2) in human epithelial caco-2 cells. J Biol Chem 276:9291–9296

    PubMed  CAS  Google Scholar 

  • Martin-Padura I, Lostaglio S, Schneemann M, Williams L, Romano M, Fruscella P, Panzeri C, Stoppacciaro A, Ruco L, Villa A, Simmons D, Dejana E (1998) Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. J Cell Biol 142:117–127

    PubMed Central  PubMed  CAS  Google Scholar 

  • Mirza M, Hreinsson J, Strand ML, Hovatta O, Soder O, Philipson L, Pettersson RF, Sollerbrant K (2006) Coxsackievirus and adenovirus receptor (CAR) is expressed in male germ cells and forms a complex with the differentiation factor JAM-C in mouse testis. Exp Cell Res 312:817–830

    PubMed  CAS  Google Scholar 

  • Mitic LL, Anderson JM (1998) Molecular architecture of tight junctions. Annu Rev Physiol 60:121–142

    PubMed  CAS  Google Scholar 

  • Mochida GH, Ganesh VS, Felie JM, Gleason D, Hill RS, Clapham KR, Rakiec D, Tan WH, Akawi N, Al-Saffar M, Partlow JN, Tinschert S, Barkovich AJ, Ali B, Al-Gazali L, Walsh CA (2010) A homozygous mutation in the tight-junction protein JAM3 causes hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. Am J Hum Genet 87:882–889

    PubMed Central  PubMed  CAS  Google Scholar 

  • Monteiro AC, Sumagin R, Rankin CR, Leoni G, Mina MJ, Reiter DM, Stehle T, Dermody TS, Schaefer SA, Hall RA, Nusrat A, Parkos CA (2013) JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and regulate epithelial barrier function. Mol Biol Cell 24:2849–2860

    PubMed Central  PubMed  CAS  Google Scholar 

  • Moog-Lutz C, Cave-Riant F, Guibal FC, Breau MA, Di Gioia Y, Couraud PO, Cayre YE, Bourdoulous S, Lutz PG (2003) JAML, a novel protein with characteristics of a junctional adhesion molecule, is induced during differentiation of myeloid leukemia cells. Blood 102:3371–3378

    PubMed  CAS  Google Scholar 

  • Muller WA (2003) Leukocyte-endothelial-cell interactions in leukocyte transmigration and the inflammatory response. Trends Immunol 24:327–334

    PubMed  CAS  Google Scholar 

  • Muller WA (2011) Mechanisms of leukocyte transendothelial migration. Annu Rev Pathol 6:323–344

    PubMed Central  PubMed  CAS  Google Scholar 

  • Murakami M, Francavilla C, Torselli I, Corada M, Maddaluno L, Sica A, Matteoli G, Iliev ID, Mantovani A, Rescigno M, Cavallaro U, Dejana E (2010) Inactivation of junctional adhesion molecule-A enhances antitumoral immune response by promoting dendritic cell and T lymphocyte infiltration. Cancer Res 70:1759–1765

    PubMed  CAS  Google Scholar 

  • Nagai-Tamai Y, Mizuno K, Hirose T, Suzuki A, Ohno S (2002) Regulated protein-protein interaction between aPKC and PAR-3 plays an essential role in the polarization of epithelial cells. Genes Cells 7:1161–1171

    PubMed  CAS  Google Scholar 

  • Nagamatsu G, Ohmura M, Mizukami T, Hamaguchi I, Hirabayashi S, Yoshida S, Hata Y, Suda T, Ohbo K (2006) A CTX family cell adhesion molecule, JAM4, is expressed in stem cell and progenitor cell populations of both male germ cell and hematopoietic cell lineages. Mol Cell Biol 26:8498–8506

    PubMed Central  PubMed  CAS  Google Scholar 

  • Nagy Z, Peters H, Huttner I (1984) Fracture faces of cell junctions in cerebral endothelium during normal and hyperosmotic conditions. Lab Investig 50:313–322

    PubMed  CAS  Google Scholar 

  • Naik MU, Mousa SA, Parkos CA, Naik UP (2003) Signaling through JAM-1 and alphavbeta3 is required for the angiogenic action of bFGF: dissociation of the JAM-1 and alphavbeta3 complex. Blood 102:2108–2114

    PubMed  CAS  Google Scholar 

  • Nasdala I, Wolburg-Buchholz K, Wolburg H, Kuhn A, Ebnet K, Brachtendorf G, Samulowitz U, Kuster B, Engelhardt B, Vestweber D, Butz S (2002) A transmembrane tight junction protein selectively expressed on endothelial cells and platelets. J Biol Chem 277:16294–16303

    PubMed  CAS  Google Scholar 

  • Noutsias M, Fechner H, de Jonge H, Wang X, Dekkers D, Houtsmuller AB, Pauschinger M, Bergelson J, Warraich R, Yacoub M, Hetzer R, Lamers J, Schultheiss HP, Poller W (2001) Human coxsackie-adenovirus receptor is colocalized with integrins alpha(v)beta(3) and alpha(v)beta(5) on the cardiomyocyte sarcolemma and upregulated in dilated cardiomyopathy: implications for cardiotropic viral infections. Circulation 104:275–280

    PubMed  CAS  Google Scholar 

  • Orlova VV, Economopoulou M, Lupu F, Santoso S, Chavakis T (2006) Junctional adhesion molecule-C regulates vascular endothelial permeability by modulating VE-cadherin-mediated cell-cell contacts. J Exp Med 203:2703–2714

    PubMed Central  PubMed  CAS  Google Scholar 

  • Ostermann G, Weber KS, Zernecke A, Schroder A, Weber C (2002) JAM-1 is a ligand of the beta(2) integrin LFA-1 involved in transendothelial migration of leukocytes. Nat Immunol 3:151–158

    PubMed  CAS  Google Scholar 

  • Ozaki H, Ishii K, Horiuchi H, Arai H, Kawamoto T, Okawa K, Iwamatsu A, Kita T (1999) Cutting edge: combined treatment of TNF-alpha and IFN-gamma causes redistribution of junctional adhesion molecule in human endothelial cells. J Immunol 163:553–557

    PubMed  CAS  Google Scholar 

  • Padden M, Leech S, Craig B, Kirk J, Brankin B, McQuaid S (2007) Differences in expression of junctional adhesion molecule-A and beta-catenin in multiple sclerosis brain tissue: increasing evidence for the role of tight junction pathology. Acta Neuropathol 113:177–186

    PubMed  CAS  Google Scholar 

  • Palmeri D, van Zante A, Huang CC, Hemmerich S, Rosen SD (2000) Vascular endothelial junction-associated molecule, a novel member of the immunoglobulin superfamily, is localized to intercellular boundaries of endothelial cells. J Biol Chem 275:19139–19145

    PubMed  CAS  Google Scholar 

  • Prota AE, Campbell JA, Schelling P, Forrest JC, Watson MJ, Peters TR, Aurrand-Lions M, Imhof BA, Dermody TS, Stehle T (2003) Crystal structure of human junctional adhesion molecule 1: implications for reovirus binding. Proc Natl Acad Sci USA 100:5366–5371

    PubMed Central  PubMed  CAS  Google Scholar 

  • Rabquer BJ, Pakozdi A, Michel JE, Gujar BS, Haines GK 3rd, Imhof BA, Koch AE (2008) Junctional adhesion molecule C mediates leukocyte adhesion to rheumatoid arthritis synovium. Arthritis Rheum 58:3020–3029

    PubMed Central  PubMed  CAS  Google Scholar 

  • Rabquer BJ, Amin MA, Teegala N, Shaheen MK, Tsou PS, Ruth JH, Lesch CA, Imhof BA, Koch AE (2010) Junctional adhesion molecule-C is a soluble mediator of angiogenesis. J Immunol 185:1777–1785

    PubMed Central  PubMed  CAS  Google Scholar 

  • Reese TS, Karnovsky MJ (1967) Fine structural localization of a blood–brain barrier to exogenous peroxidase. J Cell Biol 34:207–217

    PubMed Central  PubMed  CAS  Google Scholar 

  • Rubin LL, Hall DE, Porter S, Barbu K, Cannon C, Horner HC, Janatpour M, Liaw CW, Manning K, Morales J et al (1991) A cell culture model of the blood–brain barrier. J Cell Biol 115:1725–1735

    PubMed  CAS  Google Scholar 

  • Saitou M, Furuse M, Sasaki H, Schulzke JD, Fromm M, Takano H, Noda T, Tsukita S (2000) Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 11:4131–4142

    PubMed Central  PubMed  CAS  Google Scholar 

  • Salifu MO, Kolff Q, Murty P, Haria DM, Zimpa M, Shakeel M, Lee H, Kornecki E, Babinska A (2007) Relationship between the soluble F11 receptor and markers of inflammation in hemodialysis patients. J Investig Med 55:115–119

    PubMed  CAS  Google Scholar 

  • Santoso S, Sachs UJ, Kroll H, Linder M, Ruf A, Preissner KT, Chavakis T (2002) The junctional adhesion molecule 3 (JAM-3) on human platelets is a counterreceptor for the leukocyte integrin Mac-1. J Exp Med 196:679–691

    PubMed Central  PubMed  CAS  Google Scholar 

  • Scheiermann C, Colom B, Meda P, Patel NS, Voisin MB, Marrelli A, Woodfin A, Pitzalis C, Thiemermann C, Aurrand-Lions M, Imhof BA, Nourshargh S (2009) Junctional adhesion molecule-C mediates leukocyte infiltration in response to ischemia reperfusion injury. Arterioscler Thromb Vasc Biol 29:1509–1515

    PubMed Central  PubMed  CAS  Google Scholar 

  • Schmitt MM, Megens RT, Zernecke A, Bidzhekov K, van den Akker NM, Rademakers T, van Zandvoort MA, Hackeng TM, Koenen RR, Weber C (2013) Endothelial JAM-A guides monocytes into flow-dependent predilection sites of atherosclerosis. Circulation 24(4):217–222

    Google Scholar 

  • Shaw SK, Perkins BN, Lim YC, Liu Y, Nusrat A, Schnell FJ, Parkos CA, Luscinskas FW (2001) Reduced expression of junctional adhesion molecule and platelet/endothelial cell adhesion molecule-1 (CD31) at human vascular endothelial junctions by cytokines tumor necrosis factor-alpha plus interferon-gamma Does not reduce leukocyte transmigration under flow. Am J Pathol 159:2281–2291

    PubMed Central  PubMed  CAS  Google Scholar 

  • Shaw SK, Ma S, Kim MB, Rao RM, Hartman CU, Froio RM, Yang L, Jones T, Liu Y, Nusrat A, Parkos CA, Luscinskas FW (2004) Coordinated redistribution of leukocyte LFA-1 and endothelial cell ICAM-1 accompany neutrophil transmigration. J Exp Med 200:1571–1580

    PubMed Central  PubMed  CAS  Google Scholar 

  • Sircar M, Bradfield PF, Aurrand-Lions M, Fish RJ, Alcaide P, Yang L, Newton G, Lamont D, Sehrawat S, Mayadas T, Liang TW, Parkos CA, Imhof BA, Luscinskas FW (2007) Neutrophil transmigration under shear flow conditions in vitro is junctional adhesion molecule-C independent. J Immunol 178:5879–5887

    PubMed  CAS  Google Scholar 

  • Sobocka MB, Sobocki T, Banerjee P, Weiss C, Rushbrook JI, Norin AJ, Hartwig J, Salifu MO, Markell MS, Babinska A, Ehrlich YH, Kornecki E (2000) Cloning of the human platelet F11 receptor: a cell adhesion molecule member of the immunoglobulin superfamily involved in platelet aggregation. Blood 95:2600–2609

    PubMed  CAS  Google Scholar 

  • Sollerbrant K, Raschperger E, Mirza M, Engstrom U, Philipson L, Ljungdahl PO, Pettersson RF (2003) The Coxsackievirus and adenovirus receptor (CAR) forms a complex with the PDZ domain-containing protein ligand-of-numb protein-X (LNX). J Biol Chem 278:7439–7444

    PubMed  CAS  Google Scholar 

  • Stalker TJ, Wu J, Morgans A, Traxler EA, Wang L, Chatterjee MS, Lee D, Quertermous T, Hall RA, Hammer DA, Diamond SL, Brass LF (2009) Endothelial cell specific adhesion molecule (ESAM) localizes to platelet-platelet contacts and regulates thrombus formation in vivo. J Thromb Haemost 7:1886–1896

    PubMed  CAS  Google Scholar 

  • Suzuki A, Ohno S (2006) The PAR-aPKC system: lessons in polarity. J Cell Sci 119:979–987

    PubMed  CAS  Google Scholar 

  • Suzuki A, Yamanaka T, Hirose T, Manabe N, Mizuno K, Shimizu M, Akimoto K, Izumi Y, Ohnishi T, Ohno S (2001) 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 152:1183–1196

    PubMed Central  PubMed  CAS  Google Scholar 

  • Suzuki A, Ishiyama C, Hashiba K, Shimizu M, Ebnet K, Ohno S (2002) aPKC kinase activity is required for the asymmetric differentiation of the premature junctional complex during epithelial cell polarization. J Cell Sci 115:3565–3573

    PubMed  CAS  Google Scholar 

  • Tao-Cheng JH, Nagy Z, Brightman MW (1987) Tight junctions of brain endothelium in vitro are enhanced by astroglia. J Neurosci 7:3293–3299

    PubMed  CAS  Google Scholar 

  • Tomko RP, Johansson CB, Totrov M, Abagyan R, Frisen J, Philipson L (2000) Expression of the adenovirus receptor and its interaction with the fiber knob. Exp Cell Res 255:47–55

    PubMed  CAS  Google Scholar 

  • Tsukita S, Furuse M, Itoh M (2001) Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2:285–293

    PubMed  CAS  Google Scholar 

  • Van Itallie CM, Anderson JM (2006) Claudins and epithelial paracellular transport. Annu Rev Physiol 68:403–429

    PubMed  Google Scholar 

  • Vorbrodt AW, Dobrogowska DH (2004) Molecular anatomy of interendothelial junctions in human blood–brain barrier microvessels. Folia Histochem Cytobiol 42:67–75

    PubMed  CAS  Google Scholar 

  • Wegmann F, Ebnet K, Pasquier LD, Vestweber D, Butz S (2004) Endothelial adhesion molecule ESAM binds directly to the multidomain adaptor MAGI-1 and recruits it to cell contacts. Exp Cell Res 300:121–133

    PubMed  CAS  Google Scholar 

  • Wegmann F, Petri B, Khandoga AG, Moser C, Khandoga A, Volkery S, Li H, Nasdala I, Brandau O, Fassler R, Butz S, Krombach F, Vestweber D (2006) ESAM supports neutrophil extravasation, activation of Rho, and VEGF-induced vascular permeability. J Exp Med 203:1671–1677

    PubMed Central  PubMed  CAS  Google Scholar 

  • Williams AF, Barclay AN (1988) The immunoglobulin superfamily–domains for cell surface recognition. Annu Rev Immunol 6:381–405

    PubMed  CAS  Google Scholar 

  • Williams DW, Calderon TM, Lopez L, Carvallo-Torres L, Gaskill PJ, Eugenin EA, Morgello S, Berman JW (2013) Mechanisms of HIV Entry into the CNS: increased sensitivity of HIV infected CD14(+)CD16(+) monocytes to CCL2 and key roles of CCR2, JAM-A, and ALCAM in diapedesis. PLoS ONE 8:e69270

    PubMed Central  PubMed  CAS  Google Scholar 

  • Wolburg H, Lippoldt A (2002) Tight junctions of the blood–brain barrier: development, composition and regulation. Vasc Pharmacol 38:323–337

    CAS  Google Scholar 

  • Wolburg H, Neuhaus J, Kniesel U, Krauss B, Schmid EM, Ocalan M, Farrell C, Risau W (1994) Modulation of tight junction structure in blood–brain barrier endothelial cells. Effects of tissue culture, second messengers and cocultured astrocytes. J Cell Sci 107(Pt 5):1347–1357

    PubMed  CAS  Google Scholar 

  • Wong AD, Ye M, Levy AF, Rothstein JD, Bergles DE, Searson PC (2013) The blood–brain barrier: an engineering perspective. Front Neuroenerg 6:7

    Google Scholar 

  • Woodfin A, Reichel CA, Khandoga A, Corada M, Voisin MB, Scheiermann C, Haskard DO, Dejana E, Krombach F, Nourshargh S (2007) JAM-A mediates neutrophil transmigration in a stimulus-specific manner in vivo: evidence for sequential roles for JAM-A and PECAM-1 in neutrophil transmigration. Blood 110:1848–1856

    PubMed  CAS  Google Scholar 

  • Woodfin A, Voisin MB, Imhof BA, Dejana E, Engelhardt B, Nourshargh S (2009) Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM-2, JAM-A, and PECAM-1. Blood 113:6246–6257

    PubMed Central  PubMed  CAS  Google Scholar 

  • Woodfin A, Voisin MB, Beyrau M, Colom B, Caille D, Diapouli FM, Nash GB, Chavakis T, Albelda SM, Rainger GE, Meda P, Imhof BA, Nourshargh S (2011) The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo. Nat Immunol 12:761–769

    PubMed Central  PubMed  CAS  Google Scholar 

  • Wyss L, Schafer J, Liebner S, Mittelbronn M, Deutsch U, Enzmann G, Adams RH, Aurrand-Lions M, Plate KH, Imhof BA, Engelhardt B (2012) Junctional adhesion molecule (JAM)-C deficient C57BL/6 mice develop a severe hydrocephalus. PLoS ONE 7:e45619

    PubMed Central  PubMed  CAS  Google Scholar 

  • Yamanaka T, Horikoshi Y, Suzuki A, Sugiyama Y, Kitamura K, Maniwa R, Nagai Y, Yamashita A, Hirose T, Ishikawa H, Ohno S (2001) PAR-6 regulates aPKC activity in a novel way and mediates cell-cell contact-induced formation of the epithelial junctional complex. Genes Cells 6:721–731

    PubMed  CAS  Google Scholar 

  • Yeung D, Manias JL, Stewart DJ, Nag S (2008) Decreased junctional adhesion molecule-A expression during blood–brain barrier breakdown. Acta Neuropathol 115:635–642

    PubMed  CAS  Google Scholar 

  • Zen K, Liu Y, McCall IC, Wu T, Lee W, Babbin BA, Nusrat A, Parkos CA (2005) Neutrophil migration across tight junctions is mediated by adhesive interactions between epithelial coxsackie and adenovirus receptor and a junctional adhesion molecule-like protein on neutrophils. Mol Biol Cell 16:2694–2703

    PubMed Central  PubMed  CAS  Google Scholar 

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Acknowledgments

Our laboratory is supported by Swiss National Science Foundation grants (31003AB_135701) and ONCOSUISSE grants (KFS 2914-02-2012) to Prof B.A. Imhof.

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  1. Department of Pathology and Immunology, CMU, University of Geneva, Geneva, Switzerland

    S. Garrido-Urbani, P. F. Bradfield & B. A. Imhof

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  1. S. Garrido-Urbani
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  2. P. F. Bradfield
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  3. B. A. Imhof
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Correspondence to S. Garrido-Urbani.

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Garrido-Urbani, S., Bradfield, P.F. & Imhof, B.A. Tight junction dynamics: the role of junctional adhesion molecules (JAMs). Cell Tissue Res 355, 701–715 (2014). https://doi.org/10.1007/s00441-014-1820-1

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