Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Involvement of nectin in the localization of junctional adhesion molecule at tight junctions

Oncogene volume 21, pages 7642–7655 (2002)Cite this article

Abstract

Junctional adhesion molecule (JAM) is a Ca2+-independent immunoglobulin-like cell–cell adhesion molecule which localizes at tight junctions (TJs). Claudin is a key cell–cell adhesion molecule that forms TJ strands at TJs. JAM is associated with claudin through their cytoplasmic tail-binding protein, ZO-1. JAM is furthermore associated with Par-3, a cell polarity protein which forms a ternary complex with Par-6 and atypical protein kinase C. Nectin is another Ca2+-independent immunoglobulin-like cell–cell adhesion molecule which localizes at adherens junctions (AJs). Nectin is associated with E-cadherin through their respective cytoplasmic tail-binding proteins, afadin and catenins, and involved in the formation of AJs cooperatively with E-cadherin. We show here that nectin is furthermore involved in the localization of JAM at TJs. During the formation of the junctional complex consisting of AJs and TJs in Madin-Darby canine kidney (MDCK) cells, JAM was recruited to the nectin-based cell–cell adhesion sites. This recruitment of JAM was inhibited by nectin inhibitors, which inhibited the trans-interaction of nectin. Microbeads coated with the extracellular fragment of nectin, that interacted with cellular nectin, also recruited JAM to the bead–MDCK cell contact sites. Furthermore, when cadherin-deficient L fibroblasts stably expressing both exogenous JAM and nectin (nectin-JAM-L cells) were co-cultured with L fibroblasts expressing only nectin (nectin-L cells), JAM was concentrated at the cell–cell adhesion sites between nectin-JAM-L and nectin-L cells without the trans-interaction of JAM. Analyses of the localization and immunoprecipitation of JAM revealed that it was associated with nectin through afadin and ZO-1. These results suggest that nectin has a role in the localization of JAM at TJs in the process of the formation of the junctional complex in epithelial cells.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10

Similar content being viewed by others

References

  • Adams CL, Chen YT, Smith SJ, Nelson WJ . 1998 J. Cell Biol. 142: 1105–1119

  • Ando-Akatsuka Y, Yonemura S, Itoh M, Furuse M, Tsukita S . 1999 J. Cell Physiol. 179: 115–125

  • Aoki J, Koike S, Ise I, Sato-Yoshida Y, Nomoto A . 1994 J. Biol. Chem. 269: 8431–8438

  • Arrate MP, Rodriguez JM, Tran TM, Brock TA, Cunningham SA . 2001 J. Biol. Chem. 276: 45826–45832

  • Asakura T, Nakanishi H, Sakisaka T, Takahashi K, Mandai K, Nishimura M, Sasaki T, Takai Y . 1999 Genes Cells. 4: 573–581

  • Aurrand-Lions M, Duncan L, Ballestrem C, Imhof BA . 2001 J. Biol. Chem. 276: 2733–2741

  • Balda MS, Gonzalez-Mariscal L, Matter K, Cereijido M, Anderson JM . 1993 J. Cell Biol. 123: 293–302

  • Barton ES, Forrest JC, Connolly JL, Chappell JD, Liu Y, Schnell FJ, Nusrat A, Parkos CA, Dermody TS . 2001 Cell 104: 441–451

  • Bazzoni G, Martinez-Estrada OM, Orsenigo F, Cordenonsi M, Citi S, Dejana E . 2000 J. Biol. Chem. 275: 20520–20526

  • Bradford MM . 1976 Anal. Biochem. 72: 248–254

  • Campadelli-Fiume G, Cocchi F, Menotti L, Lopez M . 2000 Rev. Med. Virol. 10: 305–319

  • Cocchi F, Lopez M, Menotti L, Aoubala M, Dubreuil P, Campadelli-Fiume G . 1998 Proc. Natl. Acad. Sci. USA. 95: 15700–15705

  • Cocchi F, Menotti L, Dubreuil P, Lopez M, Campadelli-Fiume G . 2000 J. Virol. 74: 3909–3917

  • Cunningham SA, Arrate MP, Rodriguez JM, Bjercke RJ, Vanderslice P, Morris AP, Brock TA . 2000 J. Biol. Chem. 275: 34750–34756

  • Eberle F, Dubreuil P, Mattei MG, Devilard E, Lopez M . 1995 Gene 159: 267–272

  • Ebnet K, Schulz CU, Meyer Zu Brickwedde MK, Pendl GG, Vestweber D . 2000 J. Biol. Chem. 275: 27979–27988

  • Ebnet K, Suzuki A, Horikoshi Y, Hirose T, Meyer Zu Brickwedde MK, Ohno S, Vestweber D . 2001 EMBO J. 20: 3738–3748

  • Furuse M, Itoh M, Hirase T, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S . 1994 J. Cell Biol. 127: 1617–1626

  • Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S . 1998a J. Cell Biol. 141: 1539–1550

  • Furuse M, Sasaki H, Fujimoto K, Tsukita S . 1998b J. Cell Biol. 143: 391–401

  • Geiger B, Ginsberg D . 1991 Cell Motil. Cytoskeleton. 20: 1–6

  • Geraghty RJ, Krummenacher C, Cohen GH, Eisenberg RJ, Spear PG . 1998 Science 280: 1618–1620

  • Gumbiner B, Simons K . 1986 J. Cell Biol. 102: 457–468

  • Gumbiner B, Stevenson B, Grimaldi A . 1988 J. Cell Biol. 107: 1575–1587

  • Gumbiner BM . 1996 Cell 84: 345–357

  • Gumbiner BM . 2000 J. Cell Biol. 148: 399–403

  • Haskins J, Gu L, Wittchen ES, Hibbard J, Stevenson BR . 1998 J. Cell Biol. 141: 199–208

  • Ikeda W, Nakanishi H, Miyoshi J, Mandai K, Ishizaki H, Tanaka M, Togawa A, Takahashi K, Nishioka H, Yoshida H, Mizoguchi A, Nishikawa S, Takai Y . 1999 J. Cell Biol. 146: 1117–1132

  • Itoh M, Nagafuchi A, Yonemura S, Kitani-Yasuda T, Tsukita S, Tsukita S . 1993 J. Cell Biol. 121: 491–502

  • Itoh M, Nagafuchi A, Moroi S, Tsukita S . 1997 J. Cell Biol. 138: 181–192

  • Itoh M, Morita K, Tsukita S . 1999a J. Biol. Chem. 274: 5981–5986

  • Itoh M, Furuse M, Morita K, Kubota K, Saitou M, Tsukita S . 1999b J. Cell Biol. 147: 1351–1363

  • Itoh M, Sasaki H, Furuse M, Ozaki H, Kita T, Tsukita S . 2001 J. Cell Biol. 154: 491–498

  • Kartenbeck J, Schmelz M, Franke WW, Geiger B . 1991 J. Cell Biol. 113: 881–892

  • Laemmli UK . 1970 Nature 227: 680–685

  • Liu Y, Nusrat A, Schnell FJ, Reaves TA, Walsh S, Pochet M, Parkos CA . 2000 J. Cell Sci. 113: 2363–2374

  • Lopez M, Eberle F, Mattei MG, Gabert J, Birg F, Bardin F, Maroc C, Dubreuil P . 1995 Gene 155: 261–265

  • Lopez M, Aoubala M, Jordier F, Isnardon D, Gomez S, Dubreuil P . 1998 Blood 92: 4602–4611

  • Lopez M, Cocchi F, Menotti L, Avitabile E, Dubreuil P, Campadelli-Fiume G . 2000 J. Virol. 74: 1267–1274

  • Mandai K, Nakanishi H, Satoh A, Obaishi H, Wada M, Nishioka H, Itoh M, Mizoguchi A, Aoki T, Fujimoto T, Matsuda Y, Tsukita S, Takai Y . 1997 J. Cell Biol. 139: 517–528

  • Mandai K, Nakanishi H, Satoh A, Takahashi K, Satoh K, Nishioka H, Mizoguchi A, Takai Y . 1999 J. Cell Biol. 144: 1001–1017

  • 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 J. Cell Biol. 142: 117–127

  • Miyahara M, Nakanishi H, Takahashi K, Satoh-Horikawa K, Tachibana K, Takai Y . 2000 J. Biol. Chem. 275: 613–618

  • Mizoguchi A, Nakanishi H, Kimura K, Matsubara K, Ozaki-Kuroda K, Katata T, Honda T, Kiyohara Y, Heo K, Higashi M, Tsutsumi T, Sonoda S, Ide C, Takai Y . 2002 J. Cell Biol. 156: 555–565

  • Morrison ME, Racaniello VR . 1992 J. Virol. 66: 2807–2813

  • Nagafuchi A, Takeichi M, Tsukita S . 1991 Cell 65: 849–857

  • Nishioka H, Mizoguchi A, Nakanishi H, Mandai K, Takahashi K, Kimura K, Satoh-Moriya A, Takai Y . 2000 J. Comp. Neurol. 424: 297–306

  • Ostermann G, Weber KS, Zernecke A, Schroder A, Weber C . 2002 Nat. Immunol. 3: 151–158

  • Ozaki H, Ishii K, Horiuchi H, Arai H, Kawamoto T, Okawa K, Iwamatsu A, Kita T . 1999 J. Immunol. 163: 553–557

  • Ozaki-Kuroda K, Nakanishi H, Ohta H, Tanaka H, Kurihara H, Mueller S, Irie K, Ikeda W, Sakai T, Wimmer E, Nishimune Y, Takai Y . 2002 Curr. Biol. 12: 1145–1150

  • Ozawa M, Baribault H, Kemler R . 1989 EMBO J. 8: 1711–1717

  • Palmeri D, van Zante A, Huang CC, Hemmerich S, Rosen SD . 2000 J. Biol. Chem. 275: 19139–19145

  • Pasdar M, Nelson WJ . 1988a J. Cell Biol. 106: 677–685

  • Pasdar M, Nelson WJ . 1988b J. Cell Biol. 106: 687–695

  • Prasad R, Gu Y, Alder H, Nakamura T, Canaani O, Saito H, Huebner K, Gale RP, Nowell PC, Kuriyama K, Miyazaki Y, Croce CM, Canaani E . 1993 Cancer Res. 53: 5624–5628

  • Reymond N, Fabre S, Lecocq E, Adelaide J, Dubreuil P, Lopez M . 2001 J. Biol. Chem. 276: 43205–43215

  • Sakisaka T, Nakanishi H, Takahashi K, Mandai K, Miyahara M, Satoh A, Takaishi K, Takai Y . 1999 Oncogene 18: 1609–1617

  • Sakisaka T, Taniguchi T, Nakanishi H, Takahashi K, Miyahara M, Ikeda W, Yokoyama S, Peng YF, Yamanishi K, Takai Y . 2001 J. Virol. 75: 4734–4743

  • Satoh-Horikawa K, Nakanishi H, Takahashi K, Miyahara M, Nishimura M, Tachibana K, Mizoguchi A, Takai Y . 2000 J. Biol. Chem. 275: 10291–10299

  • Siliciano JD, Goodenough DA . 1988 J. Cell Biol. 107: 2389–2399

  • Spear PG, Eisenberg RJ, Cohen GH . 2000 Virology 275: 1–8

  • Suzuki K, Hu D, Bustos T, Zlotogora J, Richieri-Costa A, Helms JA, Spritz RA . 2000 Nat. Genet. 25: 427–430

  • Tachibana K, Nakanishi H, Mandai K, Ozaki K, Ikeda W, Yamamoto Y, Nagafuchi A, Tsukita S, Takai Y . 2000 J. Cell Biol. 150: 1161–1176

  • Takahashi K, Nakanishi H, Miyahara M, Mandai K, Satoh K, Satoh A, Nishioka H, Aoki J, Nomoto A, Mizoguchi A, Takai Y . 1999 J. Cell Biol. 145: 539–549

  • Takeichi M . 1988 Development 102: 639–655

  • Takeichi M . 1991 Science 251: 1451–1455

  • Tsukita S, Tsukita S, Nagafuchi A, Yonemura S . 1992 Curr. Opin. Cell Biol. 4: 834–839

  • Tsukita S, Furuse M . 1999 Trends. Cell Biol. 9: 268–273

  • Tsukita S, Furuse M, Itoh M . 1999 Curr. Opin. Cell Biol. 11: 628–633

  • Vasioukhin V, Bauer C, Yin M, Fuchs E . 2000 Cell 100: 209–219

  • Warner MS, Geraghty RJ, Martinez WM, Montgomery RI, Whitbeck JC, Xu R, Eisenberg RJ, Cohen GH, Spear PG . 1998 Virology 246: 179–189

  • Watabe M, Nagafuchi A, Tsukita S, Takeichi M . 1994 J. Cell Biol. 127: 247–256

  • Watabe-Uchida M, Uchida N, Imamura Y, Nagafuchi A, Fujimoto K, Uemura T, Vermeulen S, van Roy F, Adamson ED, Takeichi M . 1998 J. Cell Biol. 142: 847–857

  • Willott E, Balda MS, Fanning AS, Jameson B, Van Itallie C, Anderson JM . 1993 Proc. Natl. Acad. Sci. USA 90: 7834–7838

  • Wittchen ES, Haskins J, Stevenson BR . 1999 J. Biol. Chem. 274: 35179–35185

  • Wittchen ES, Haskins J, Stevenson BR . 2000 J. Cell Biol. 151: 825–836

  • Yokoyama S, Tachibana K, Nakanishi H, Yamamoto Y, Irie K, Mandai K, Nagafuchi A, Monden M, Takai Y . 2001 Mol. Biol. Cell 12: 1595–1609

  • Yonemura S, Itoh M, Nagafuchi A, Tsukita S . 1995 J. Cell Sci. 108: 127–142

Download references

Acknowledgements

We thank Dr M Takeichi (Center for Developmental Biology, RIKEN, Kobe, Japan) for providing us with the anti-E-cadherin mAb, Dr Sh Tsukita (Kyoto University, Kyoto, Japan) for providing us with the JAM-L and JAM-ΔC-L cells and the anti-ZO-1 mAb, and Dr W Birchmeier (Max-Delbruck-Center for Molecular Medicine, Berlin, Germany) for providing us with MDCK cells. The investigation at Osaka University Medical School was supported by grants-in-aid for Scientific Research and for Cancer Research from the Ministry of Education, Science, Sports, Culture, and Technology, Japan (2000, 2001).

Author information

Authors and Affiliations

  1. Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, 565-0871, Japan

    Atsunori Fukuhara, Kenji Irie, Hiroyuki Nakanishi, Kyoji Takekuni, Tomomi Kawakatsu, Wataru Ikeda, Akio Yamada, Tatsuo Katata, Tomoyuki Honda, Tatsuhiro Sato, Kazuya Shimizu & Yoshimi Takai

  2. Department of Geriatric Medicine, Faculty of Medicine, Kyoto University, Kyoto, 606-8501, Japan

    Harunobu Ozaki, Hisanori Horiuchi & Toru Kita

Authors
  1. Atsunori Fukuhara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenji Irie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiroyuki Nakanishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kyoji Takekuni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tomomi Kawakatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wataru Ikeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Akio Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tatsuo Katata
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tomoyuki Honda
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tatsuhiro Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kazuya Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Harunobu Ozaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Hisanori Horiuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Toru Kita
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Yoshimi Takai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshimi Takai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fukuhara, A., Irie, K., Nakanishi, H. et al. Involvement of nectin in the localization of junctional adhesion molecule at tight junctions. Oncogene 21, 7642–7655 (2002). https://doi.org/10.1038/sj.onc.1205875

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205875

Keywords

This article is cited by

Search

Advanced search

Quick links