The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

TJP1  -  tight junction protein 1 (zona occludens 1)

Canis lupus familiaris

Synonyms: ZO-1, ZO1
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of TJP1

  • MDCK cells permanently transformed with Moloney sarcoma virus, which expresses low levels of E-cadherin, displayed clusters of cytoplasmic ZO-1 granules and very little of this protein at the cell surface [1].
  • Upon transfection with E-cadherin into Moloney sarcoma virus-MDCK cells, ZO-1 redistributed to E-cadherin-rich lateral plasma membrane but later failed to segregate into mature tight junctions [1].
  • Recently, with the use of an ATP depletion-repletion model for ischemia and reperfusion injury in Madin-Darby canine kidney cells, TJ proteins such as zonula occludens-1 (ZO-1) were shown to reversibly form large complexes and associate with cytoskeletal proteins (T. Tsukamoto and S. K. Nigam, J. Biol. Chem. 272: 16133-16139, 1997) [2].

High impact information on TJP1

  • 48 h after Ca2+ switch, upon complete polarization of the epithelium, most of the ZO-1 had segregated from lateral E-cadherin and formed a distinct, separate apical ring [1].
  • In MDCK cells cultured in low (micromolar) calcium levels, the tight junctional protein Zonula Occludens-1 (ZO-1) is distributed intracellularly in granular clusters, the larger of which codistribute with E-cadherin [1].
  • 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 [3].
  • 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 [3].
  • We present evidence that under certain conditions of cell growth, ZO-1 can be detected in the nucleus [3].

Biological context of TJP1

  • Accordingly, we have sequenced ZO-1 in this cell type, because this protein is involved in the response of the TJ to changes in Ca2+, phosphorylation, and the cytoskeleton [4].
  • ZO-1 of MDCK cells comprises 6805 bp with a predicted open reading frame of 1769 amino acids [4].
  • Two exonic elements in the flanking constitutive exons control the alternative splicing of the alpha exon of the ZO-1 pre-mRNA [5].
  • Staining of the tight junction-associated protein ZO-1 showed that the changes in transepithelial electrical resistance were accompanied by a diffusing of the protein away from cell peripheries and a reconcentration to the tight junction areas following resistance recovery [6].

Anatomical context of TJP1

  • Moreover, membrane-associated PKC activity more than doubled during junction assembly, and immunocytochemical analysis revealed a pool of PKC zeta that appeared to colocalize with ZO-1 at the tight junction [7].
  • Moreover, the apical structure of filamentous actin (F-actin) was disturbed and tight junction-associated proteins (ZO-1 and occludin) were dispersed along the basolateral membranes [8].
  • The C-terminus of Cx43 has been shown to interact with the PDZ2 domain of the tight and adherens junction associated zona occludens 1 (ZO-1) protein [9].

Associations of TJP1 with chemical compounds

  • We found two new splicing regions at the proline-rich region: beta had not been reported in human and mouse counterparts, and gamma, which was previously sequenced in human and mouse ZO-1, is now identified as a splicing region [4].
  • The mass of this complex and the incorporation of ZO-1 into the Triton X-100-insoluble cytoskeleton were not PKC dependent [7].
  • 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 [3].
  • In addition, ZO-1 was phosphorylated subsequent to the initiation of cell-cell contact, and treatment with calphostin C prevented approximately 85% of the phosphorylation increase [7].
  • The utility for membrane proteins present in small numbers of copies is demonstrated by labeling a glutamate receptor subunit in mouse cerebellar cortex and the ZO-1 protein in tight junctions between MDCK cells [10].

Analytical, diagnostic and therapeutic context of TJP1

  • With the information provided by the sequence, Southern blot, and PCR experiments we can predict a single genomic copy of MDCK-ZO-1 that is at least 13.16 kb long [4].
  • Immunofluorescence and immunoelectron microscopy confirmed a close association of beta-catenin and ZO-1 at 0 and 2 h after Ca2+ switch [1].
  • Immunoprecipitation with ZO-1 antibodies of extracts from cells kept in low calcium and 2 h after shifting to 1.8 mM Ca2+ demonstrated the association of ZO-1 with alpha-, beta-, and gamma-catenins [1].
  • Two different antibodies against distinct portions of the ZO-1 polypeptide reveal nuclear staining in subconfluent, but not confluent, cell cultures [3].
  • In Galpha(12)-expressing cells, we found that ZO-1 and Galpha(12) co-localize by confocal microscopy and co-immunoprecipitate [11].


  1. Catenins and zonula occludens-1 form a complex during early stages in the assembly of tight junctions. Rajasekaran, A.K., Hojo, M., Huima, T., Rodriguez-Boulan, E. J. Cell Biol. (1996) [Pubmed]
  2. A role for intracellular calcium in tight junction reassembly after ATP depletion-repletion. Ye, J., Tsukamoto, T., Sun, A., Nigam, S.K. Am. J. Physiol. (1999) [Pubmed]
  3. The junction-associated protein, zonula occludens-1, localizes to the nucleus before the maturation and during the remodeling of cell-cell contacts. Gottardi, C.J., Arpin, M., Fanning, A.S., Louvard, D. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  4. Molecular characterization of the tight junction protein ZO-1 in MDCK cells. González-Mariscal, L., Islas, S., Contreras, R.G., García-Villegas, M.R., Betanzos, A., Vega, J., Diaz-Quiñónez, A., Martín-Orozco, N., Ortiz-Navarrete, V., Cereijido, M., Valdés, J. Exp. Cell Res. (1999) [Pubmed]
  5. Two exonic elements in the flanking constitutive exons control the alternative splicing of the alpha exon of the ZO-1 pre-mRNA. Martínez-Contreras, R., Galindo, J.M., Aguilar-Rojas, A., Valdés, J. Biochim. Biophys. Acta (2003) [Pubmed]
  6. Effect of FCCP on tight junction permeability and cellular distribution of ZO-1 protein in epithelial (MDCK) cells. Li, C.X., Poznansky, M.J. Biochim. Biophys. Acta (1990) [Pubmed]
  7. Regulated assembly of tight junctions by protein kinase C. Stuart, R.O., Nigam, S.K. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  8. Apically exposed, tight junction-associated beta1-integrins allow binding and YopE-mediated perturbation of epithelial barriers by wild-type Yersinia bacteria. Tafazoli, F., Holmström, A., Forsberg, A., Magnusson, K.E. Infect. Immun. (2000) [Pubmed]
  9. Connexin43 PDZ2 binding domain mutants create functional gap junctions and exhibit altered phosphorylation. Jin, C., Martyn, K.D., Kurata, W.E., Warn-Cramer, B.J., Lau, A.F. Cell Commun. Adhes. (2004) [Pubmed]
  10. Immunoelectronmicroscopy of soluble and membrane proteins with a sensitive postembedding method. Moreira, J.E., Dodane, V., Reese, T.S. J. Histochem. Cytochem. (1998) [Pubmed]
  11. 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. Meyer, T.N., Schwesinger, C., Denker, B.M. J. Biol. Chem. (2002) [Pubmed]
WikiGenes - Universities