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Proc Natl Acad Sci U S A. Oct 1, 1996; 93(20): 10779–10784.
PMCID: PMC38232

The junction-associated protein, zonula occludens-1, localizes to the nucleus before the maturation and during the remodeling of cell-cell contacts.

Abstract

The junction-associated protein zonula occludens-1 (ZO-1) is a member of a family of membrane-associated guanylate kinase homologues thought to be important in signal transduction at sites of cell-cell contact. We present evidence that under certain conditions of cell growth, ZO-1 can be detected in the nucleus. Two different antibodies against distinct portions of the ZO-1 polypeptide reveal nuclear staining in subconfluent, but not confluent, cell cultures. An exogenously expressed, epitope-tagged ZO-1 can also be detected in the nuclei of transfected cells. Nuclear accumulation can be stimulated at sites of wounding in cultured epithelial cells, and immunoperoxidase detection of ZO-1 in tissue sections of intestinal epithelial cells reveals nuclear labeling only along the outer tip of the villus. These results suggest that the nuclear localization of ZO-1 is inversely related to the extent and/or maturity of cell contact. Since cell-cell contacts are specialized sites for signaling pathways implicated in growth and differentiation, we suggest that the nuclear accumulation of ZO-1 may be relevant for its suggested role in membrane-associated guanylate kinase homologue signal transduction.

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  • Stevenson BR, Siliciano JD, Mooseker MS, Goodenough DA. Identification of ZO-1: a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia. J Cell Biol. 1986 Sep;103(3):755–766. [PMC free article] [PubMed]
  • Balda MS, Anderson JM. Two classes of tight junctions are revealed by ZO-1 isoforms. Am J Physiol. 1993 Apr;264(4 Pt 1):C918–C924. [PubMed]
  • Howarth AG, Hughes MR, Stevenson BR. Detection of the tight junction-associated protein ZO-1 in astrocytes and other nonepithelial cell types. Am J Physiol. 1992 Feb;262(2 Pt 1):C461–C469. [PubMed]
  • Itoh M, Nagafuchi A, Yonemura S, Kitani-Yasuda T, Tsukita S, Tsukita S. The 220-kD protein colocalizing with cadherins in non-epithelial cells is identical to ZO-1, a tight junction-associated protein in epithelial cells: cDNA cloning and immunoelectron microscopy. J Cell Biol. 1993 May;121(3):491–502. [PMC free article] [PubMed]
  • Gumbiner B, Stevenson B, Grimaldi A. The role of the cell adhesion molecule uvomorulin in the formation and maintenance of the epithelial junctional complex. J Cell Biol. 1988 Oct;107(4):1575–1587. [PMC free article] [PubMed]
  • Siliciano JD, Goodenough DA. Localization of the tight junction protein, ZO-1, is modulated by extracellular calcium and cell-cell contact in Madin-Darby canine kidney epithelial cells. J Cell Biol. 1988 Dec;107(6 Pt 1):2389–2399. [PMC free article] [PubMed]
  • Balda MS, González-Mariscal L, Contreras RG, Macias-Silva M, Torres-Marquez ME, García-Sáinz JA, Cereijido M. Assembly and sealing of tight junctions: possible participation of G-proteins, phospholipase C, protein kinase C and calmodulin. J Membr Biol. 1991 Jun;122(3):193–202. [PubMed]
  • Willott E, Balda MS, Fanning AS, Jameson B, Van Itallie C, Anderson JM. The tight junction protein ZO-1 is homologous to the Drosophila discs-large tumor suppressor protein of septate junctions. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7834–7838. [PMC free article] [PubMed]
  • Woods DF, Bryant PJ. The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions. Cell. 1991 Aug 9;66(3):451–464. [PubMed]
  • Jesaitis LA, Goodenough DA. Molecular characterization and tissue distribution of ZO-2, a tight junction protein homologous to ZO-1 and the Drosophila discs-large tumor suppressor protein. J Cell Biol. 1994 Mar;124(6):949–961. [PMC free article] [PubMed]
  • Cho KO, Hunt CA, Kennedy MB. The rat brain postsynaptic density fraction contains a homolog of the Drosophila discs-large tumor suppressor protein. Neuron. 1992 Nov;9(5):929–942. [PubMed]
  • Kistner U, Wenzel BM, Veh RW, Cases-Langhoff C, Garner AM, Appeltauer U, Voss B, Gundelfinger ED, Garner CC. SAP90, a rat presynaptic protein related to the product of the Drosophila tumor suppressor gene dlg-A. J Biol Chem. 1993 Mar 5;268(7):4580–4583. [PubMed]
  • Ruff P, Speicher DW, Husain-Chishti A. Molecular identification of a major palmitoylated erythrocyte membrane protein containing the src homology 3 motif. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6595–6599. [PMC free article] [PubMed]
  • Kim SK. Tight junctions, membrane-associated guanylate kinases and cell signaling. Curr Opin Cell Biol. 1995 Oct;7(5):641–649. [PubMed]
  • Lue RA, Marfatia SM, Branton D, Chishti AH. Cloning and characterization of hdlg: the human homologue of the Drosophila discs large tumor suppressor binds to protein 4.1. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9818–9822. [PMC free article] [PubMed]
  • Kim E, Niethammer M, Rothschild A, Jan YN, Sheng M. Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases. Nature. 1995 Nov 2;378(6552):85–88. [PubMed]
  • Kornau HC, Schenker LT, Kennedy MB, Seeburg PH. Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science. 1995 Sep 22;269(5231):1737–1740. [PubMed]
  • Anderson JM, Balda MS, Fanning AS. The structure and regulation of tight junctions. Curr Opin Cell Biol. 1993 Oct;5(5):772–778. [PubMed]
  • Arpin M, Friederich E, Algrain M, Vernel F, Louvard D. Functional differences between L- and T-plastin isoforms. J Cell Biol. 1994 Dec;127(6 Pt 2):1995–2008. [PMC free article] [PubMed]
  • Brewer CB, Roth MG. A single amino acid change in the cytoplasmic domain alters the polarized delivery of influenza virus hemagglutinin. J Cell Biol. 1991 Aug;114(3):413–421. [PMC free article] [PubMed]
  • Einberger H, Mertz R, Hofschneider PH, Neubert WJ. Purification, renaturation, and reconstituted protein kinase activity of the Sendai virus large (L) protein: L protein phosphorylates the NP and P proteins in vitro. J Virol. 1990 Sep;64(9):4274–4280. [PMC free article] [PubMed]
  • Willott E, Balda MS, Heintzelman M, Jameson B, Anderson JM. Localization and differential expression of two isoforms of the tight junction protein ZO-1. Am J Physiol. 1992 May;262(5 Pt 1):C1119–C1124. [PubMed]
  • Kreis TE. Microtubules containing detyrosinated tubulin are less dynamic. EMBO J. 1987 Sep;6(9):2597–2606. [PMC free article] [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. [PMC free article] [PubMed]
  • Lorenzen JA, Dadabay CY, Fischer EH. COOH-terminal sequence motifs target the T cell protein tyrosine phosphatase to the ER and nucleus. J Cell Biol. 1995 Nov;131(3):631–643. [PMC free article] [PubMed]
  • Gordon JI, Hermiston ML. Differentiation and self-renewal in the mouse gastrointestinal epithelium. Curr Opin Cell Biol. 1994 Dec;6(6):795–803. [PubMed]
  • Forbes DJ. Structure and function of the nuclear pore complex. Annu Rev Cell Biol. 1992;8:495–527. [PubMed]
  • Bouvier D, Baldacci G. The N-terminus of fission yeast DNA polymerase alpha contains a basic pentapeptide that acts in vivo as a nuclear localization signal. Mol Biol Cell. 1995 Dec;6(12):1697–1705. [PMC free article] [PubMed]
  • Dingwall C, Sharnick SV, Laskey RA. A polypeptide domain that specifies migration of nucleoplasmin into the nucleus. Cell. 1982 Sep;30(2):449–458. [PubMed]
  • Zhao LJ, Padmanabhan R. Nuclear transport of adenovirus DNA polymerase is facilitated by interaction with preterminal protein. Cell. 1988 Dec 23;55(6):1005–1015. [PubMed]
  • Madara JL. Maintenance of the macromolecular barrier at cell extrusion sites in intestinal epithelium: physiological rearrangement of tight junctions. J Membr Biol. 1990 Jun;116(2):177–184. [PubMed]
  • Tsukita S, Itoh M, Nagafuchi A, Yonemura S, Tsukita S. Submembranous junctional plaque proteins include potential tumor suppressor molecules. J Cell Biol. 1993 Dec;123(5):1049–1053. [PMC free article] [PubMed]
  • Schmeichel KL, Beckerle MC. The LIM domain is a modular protein-binding interface. Cell. 1994 Oct 21;79(2):211–219. [PubMed]
  • Lieber T, Kidd S, Alcamo E, Corbin V, Young MW. Antineurogenic phenotypes induced by truncated Notch proteins indicate a role in signal transduction and may point to a novel function for Notch in nuclei. Genes Dev. 1993 Oct;7(10):1949–1965. [PubMed]
  • Fortini ME, Rebay I, Caron LA, Artavanis-Tsakonas S. An activated Notch receptor blocks cell-fate commitment in the developing Drosophila eye. Nature. 1993 Oct 7;365(6446):555–557. [PubMed]
  • Struhl G, Fitzgerald K, Greenwald I. Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo. Cell. 1993 Jul 30;74(2):331–345. [PubMed]
  • Artavanis-Tsakonas S, Matsuno K, Fortini ME. Notch signaling. Science. 1995 Apr 14;268(5208):225–232. [PubMed]
  • Funayama N, Fagotto F, McCrea P, Gumbiner BM. Embryonic axis induction by the armadillo repeat domain of beta-catenin: evidence for intracellular signaling. J Cell Biol. 1995 Mar;128(5):959–968. [PMC free article] [PubMed]
  • Siegfried E, Perrimon N. Drosophila wingless: a paradigm for the function and mechanism of Wnt signaling. Bioessays. 1994 Jun;16(6):395–404. [PubMed]
  • Rajasekaran AK, Hojo M, Huima T, Rodriguez-Boulan E. Catenins and zonula occludens-1 form a complex during early stages in the assembly of tight junctions. J Cell Biol. 1996 Feb;132(3):451–463. [PMC free article] [PubMed]
  • Lee S, Chen DY, Humphrey JS, Gnarra JR, Linehan WM, Klausner RD. Nuclear/cytoplasmic localization of the von Hippel-Lindau tumor suppressor gene product is determined by cell density. Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1770–1775. [PMC free article] [PubMed]

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