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J Cell Biol. 1996 August 2; 134(4): 1003–1018.
PMCID: PMC2120966

Symplekin, a novel type of tight junction plaque protein


Using a monoclonal antibody we have identified and cDNA-cloned a novel type of protein localized, by light and electron microscopy, to the plaque associated with the cytoplasmic face of the tight junction- containing zone (zonula occludens) of polar epithelial cells and of Sertoli cells of testis, but absent from the junctions of vascular endothelia. The approximately 3.7-kb mRNA encodes a polypeptide of 1142 amino acids (calculated molecular weight 126.5 kD, pI 6.25), for which the name "symplekin" (from Greek sigma upsilon mu pi lambda epsilon kappa epsilon iota, nu, to tie together, to weave, to be intertwined) is proposed. However, both the mRNA and the protein can also be detected in a wide range of cell types that do not form tight junctions or are even completely devoid of any stable cell contacts. Careful analyses have revealed that the protein occurs in all these diverse cells in the nucleoplasm, and only in those cells forming tight junctions is it recruited, partly but specifically, to the plaque structure of the zonula occludens. We discuss symplekin as a representative of a group of dual residence proteins which occur and probably function in the nucleus as well as in the plaques exclusive for either tight junctions, adherens junctions, or desmosomes.

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Selected References

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  • Achtstaetter T, Hatzfeld M, Quinlan RA, Parmelee DC, Franke WW. Separation of cytokeratin polypeptides by gel electrophoretic and chromatographic techniques and their identification by immunoblotting. Methods Enzymol. 1986;134:355–371. [PubMed]
  • Achstätter T, Moll R, Anderson A, Kuhn C, Pitz S, Schwechheimer K, Franke WW. Expression of glial filament protein (GFP) in nerve sheaths and non-neural cells re-examined using monoclonal antibodies, with special emphasis on the co-expression of GFP and cytokeratins in epithelial cells of human salivary gland and pleomorphic adenomas. Differentiation. 1986;31(3):206–227. [PubMed]
  • Anderson JM, Stevenson BR, Jesaitis LA, Goodenough DA, Mooseker MS. Characterization of ZO-1, a protein component of the tight junction from mouse liver and Madin-Darby canine kidney cells. J Cell Biol. 1988 Apr;106(4):1141–1149. [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]
  • Byers S, Graham R, Dai HN, Hoxter B. Development of Sertoli cell junctional specializations and the distribution of the tight-junction-associated protein ZO-1 in the mouse testis. Am J Anat. 1991 May;191(1):35–47. [PubMed]
  • Citi S. The molecular organization of tight junctions. J Cell Biol. 1993 May;121(3):485–489. [PMC free article] [PubMed]
  • Citi S, Sabanay H, Jakes R, Geiger B, Kendrick-Jones J. Cingulin, a new peripheral component of tight junctions. Nature. 1988 May 19;333(6170):272–276. [PubMed]
  • Citi S, Sabanay H, Kendrick-Jones J, Geiger B. Cingulin: characterization and localization. J Cell Sci. 1989 May;93(Pt 1):107–122. [PubMed]
  • Cowin P, Kapprell HP, Franke WW. The complement of desmosomal plaque proteins in different cell types. J Cell Biol. 1985 Oct;101(4):1442–1454. [PMC free article] [PubMed]
  • Demlehner MP, Schäfer S, Grund C, Franke WW. Continual assembly of half-desmosomal structures in the absence of cell contacts and their frustrated endocytosis: a coordinated Sisyphus cycle. J Cell Biol. 1995 Nov;131(3):745–760. [PMC free article] [PubMed]
  • Franke WW, Schmid E, Vandekerckhove J, Weber K. Permanently proliferating rat vascular smooth muscle cell with maintained expression of smooth muscle characteristics, including actin of the vascular smooth muscle type. J Cell Biol. 1980 Dec;87(3 Pt 1):594–600. [PMC free article] [PubMed]
  • Franke WW, Schiller DL, Moll R, Winter S, Schmid E, Engelbrecht I, Denk H, Krepler R, Platzer B. Diversity of cytokeratins. Differentiation specific expression of cytokeratin polypeptides in epithelial cells and tissues. J Mol Biol. 1981 Dec 25;153(4):933–959. [PubMed]
  • Franke WW, Moll R, Schiller DL, Schmid E, Kartenbeck J, Mueller H. Desmoplakins of epithelial and myocardial desmosomes are immunologically and biochemically related. Differentiation. 1982;23(2):115–127. [PubMed]
  • Franke WW, Kapprell HP, Cowin P. Plakoglobin is a component of the filamentous subplasmalemmal coat of lens cells. Eur J Cell Biol. 1987 Jun;43(3):301–315. [PubMed]
  • Franke WW, Goldschmidt MD, Zimbelmann R, Mueller HM, Schiller DL, Cowin P. Molecular cloning and amino acid sequence of human plakoglobin, the common junctional plaque protein. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4027–4031. [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]
  • Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S. Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol. 1993 Dec;123(6 Pt 2):1777–1788. [PMC free article] [PubMed]
  • Gumbiner BM. Breaking through the tight junction barrier. J Cell Biol. 1993 Dec;123(6 Pt 2):1631–1633. [PMC free article] [PubMed]
  • Gumbiner B, Lowenkopf T, Apatira D. Identification of a 160-kDa polypeptide that binds to the tight junction protein ZO-1. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3460–3464. [PubMed]
  • Heid HW, Schmidt A, Zimbelmann R, Schäfer S, Winter-Simanowski S, Stumpp S, Keith M, Figge U, Schnölzer M, Franke WW. Cell type-specific desmosomal plaque proteins of the plakoglobin family: plakophilin 1 (band 6 protein). Differentiation. 1994 Dec;58(2):113–131. [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]
  • Howarth AG, Singer KL, Stevenson BR. Analysis of the distribution and phosphorylation state of ZO-1 in MDCK and nonepithelial cells. J Membr Biol. 1994 Feb;137(3):261–270. [PubMed]
  • Itoh M, Yonemura S, Nagafuchi A, Tsukita S, Tsukita S. A 220-kD undercoat-constitutive protein: its specific localization at cadherin-based cell-cell adhesion sites. J Cell Biol. 1991 Dec;115(5):1449–1462. [PMC free article] [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]
  • 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]
  • Karnovsky A, Klymkowsky MW. Anterior axis duplication in Xenopus induced by the over-expression of the cadherin-binding protein plakoglobin. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4522–4526. [PubMed]
  • Kim SK. Tight junctions, membrane-associated guanylate kinases and cell signaling. Curr Opin Cell Biol. 1995 Oct;7(5):641–649. [PubMed]
  • Knapp AC, Franke WW. Spontaneous losses of control of cytokeratin gene expression in transformed, non-epithelial human cells occurring at different levels of regulation. Cell. 1989 Oct 6;59(1):67–79. [PubMed]
  • Kozak M. The scanning model for translation: an update. J Cell Biol. 1989 Feb;108(2):229–241. [PMC free article] [PubMed]
  • Krohne G, Franke WW. A major soluble acidic protein located in nuclei of diverse vertebrate species. Exp Cell Res. 1980 Sep;129(1):167–189. [PubMed]
  • Kurihara H, Anderson JM, Farquhar MG. Diversity among tight junctions in rat kidney: glomerular slit diaphragms and endothelial junctions express only one isoform of the tight junction protein ZO-1. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7075–7079. [PubMed]
  • Madara JL. Tight junction dynamics: is paracellular transport regulated? Cell. 1988 May 20;53(4):497–498. [PubMed]
  • Melan MA, Sluder G. Redistribution and differential extraction of soluble proteins in permeabilized cultured cells. Implications for immunofluorescence microscopy. J Cell Sci. 1992 Apr;101(Pt 4):731–743. [PubMed]
  • Miragall F, Krause D, de Vries U, Dermietzel R. Expression of the tight junction protein ZO-1 in the olfactory system: presence of ZO-1 on olfactory sensory neurons and glial cells. J Comp Neurol. 1994 Mar 22;341(4):433–448. [PubMed]
  • Moll R, Franke WW, Schiller DL, Geiger B, Krepler R. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell. 1982 Nov;31(1):11–24. [PubMed]
  • Moll R, Cowin P, Kapprell HP, Franke WW. Desmosomal proteins: new markers for identification and classification of tumors. Lab Invest. 1986 Jan;54(1):4–25. [PubMed]
  • Nusrat A, Giry M, Turner JR, Colgan SP, Parkos CA, Carnes D, Lemichez E, Boquet P, Madara JL. Rho protein regulates tight junctions and perijunctional actin organization in polarized epithelia. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10629–10633. [PubMed]
  • Peifer M. Cell adhesion and signal transduction: the Armadillo connection. Trends Cell Biol. 1995 Jun;5(6):224–229. [PubMed]
  • Petrov T, Howarth AG, Krukoff TL, Stevenson BR. Distribution of the tight junction-associated protein ZO-1 in circumventricular organs of the CNS. Brain Res Mol Brain Res. 1994 Feb;21(3-4):235–246. [PubMed]
  • Pinto da Silva P, Kachar B. On tight-junction structure. Cell. 1982 Mar;28(3):441–450. [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]
  • Rose O, Grund C, Reinhardt S, Starzinski-Powitz A, Franke WW. Contactus adherens, a special type of plaque-bearing adhering junction containing M-cadherin, in the granule cell layer of the cerebellar glomerulus. Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6022–6026. [PubMed]
  • Satoh H, Zhong Y, Isomura H, Saitoh M, Enomoto K, Sawada N, Mori M. Localization of 7H6 tight junction-associated antigen along the cell border of vascular endothelial cells correlates with paracellular barrier function against ions, large molecules, and cancer cells. Exp Cell Res. 1996 Feb 1;222(2):269–274. [PubMed]
  • Schäfer S, Koch PJ, Franke WW. Identification of the ubiquitous human desmoglein, Dsg2, and the expression catalogue of the desmoglein subfamily of desmosomal cadherins. Exp Cell Res. 1994 Apr;211(2):391–399. [PubMed]
  • Schmidt A, Heid HW, Schäfer S, Nuber UA, Zimbelmann R, Franke WW. Desmosomes and cytoskeletal architecture in epithelial differentiation: cell type-specific plaque components and intermediate filament anchorage. Eur J Cell Biol. 1994 Dec;65(2):229–245. [PubMed]
  • Schnabel E, Anderson JM, Farquhar MG. The tight junction protein ZO-1 is concentrated along slit diaphragms of the glomerular epithelium. J Cell Biol. 1990 Sep;111(3):1255–1263. [PMC free article] [PubMed]
  • Schnölzer M, Alewood P, Jones A, Alewood D, Kent SB. In situ neutralization in Boc-chemistry solid phase peptide synthesis. Rapid, high yield assembly of difficult sequences. Int J Pept Protein Res. 1992 Sep-Oct;40(3-4):180–193. [PubMed]
  • Stevenson BR, Begg DA. Concentration-dependent effects of cytochalasin D on tight junctions and actin filaments in MDCK epithelial cells. J Cell Sci. 1994 Mar;107(Pt 3):367–375. [PubMed]
  • 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]
  • Strunnikov AV, Larionov VL, Koshland D. SMC1: an essential yeast gene encoding a putative head-rod-tail protein is required for nuclear division and defines a new ubiquitous protein family. J Cell Biol. 1993 Dec;123(6 Pt 2):1635–1648. [PMC free article] [PubMed]
  • Takeichi M. Morphogenetic roles of classic cadherins. Curr Opin Cell Biol. 1995 Oct;7(5):619–627. [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]
  • Van Itallie CM, Balda MS, Anderson JM. Epidermal growth factor induces tyrosine phosphorylation and reorganization of the tight junction protein ZO-1 in A431 cells. J Cell Sci. 1995 Apr;108(Pt 4):1735–1742. [PubMed]
  • Weber E, Berta G, Tousson A, St John P, Green MW, Gopalokrishnan U, Jilling T, Sorscher EJ, Elton TS, Abrahamson DR, et al. Expression and polarized targeting of a rab3 isoform in epithelial cells. J Cell Biol. 1994 May;125(3):583–594. [PMC free article] [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. [PubMed]
  • Zahraoui A, Joberty G, Arpin M, Fontaine JJ, Hellio R, Tavitian A, Louvard D. A small rab GTPase is distributed in cytoplasmic vesicles in non polarized cells but colocalizes with the tight junction marker ZO-1 in polarized epithelial cells. J Cell Biol. 1994 Jan;124(1-2):101–115. [PMC free article] [PubMed]
  • Zhong Y, Saitoh T, Minase T, Sawada N, Enomoto K, Mori M. Monoclonal antibody 7H6 reacts with a novel tight junction-associated protein distinct from ZO-1, cingulin and ZO-2. J Cell Biol. 1993 Jan;120(2):477–483. [PMC free article] [PubMed]
  • Zhong Y, Enomoto K, Isomura H, Sawada N, Minase T, Oyamada M, Konishi Y, Mori M. Localization of the 7H6 antigen at tight junctions correlates with the paracellular barrier function of MDCK cells. Exp Cell Res. 1994 Oct;214(2):614–620. [PubMed]

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