Genomes and Genes
Gene Symbol: ZO 1
Description: tight junction protein 1
Alias: ZO-1, tight junction protein ZO-1, zona occludens 1, zonula occludens 1 protein
Products: ZO 1
- Kanmogne G, Primeaux C, Grammas P. HIV-1 gp120 proteins alter tight junction protein expression and brain endothelial cell permeability: implications for the pathogenesis of HIV-associated dementia. J Neuropathol Exp Neurol. 2005;64:498-505 pubmed
- Suzuki A, Yamanaka T, Hirose T, Manabe N, Mizuno K, Shimizu M, et al. 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. 2001;152:1183-96 pubmed..These results indicate that aPKC is involved in the evolutionarily conserved PAR protein complex, and plays critical roles in the development of the junctional structures and apico-basal polarization of mammalian epithelial cells. ..
- Kausalya P, Reichert M, Hunziker W. Connexin45 directly binds to ZO-1 and localizes to the tight junction region in epithelial MDCK cells. FEBS Lett. 2001;505:92-6 pubmed..e. Cx43 and Cx45) that can associate with ZO proteins indicate that ZO proteins may play a more general role in organizing gap junctions and/or in recruiting signaling molecules that regulate intercellular communication. ..
- Fanning A, Jameson B, Jesaitis L, Anderson J. The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton. J Biol Chem. 1998;273:29745-53 pubmed..These observations suggest that one functional role of ZO-1 is to organize components of the tight junction and link them to the cortical actin cytoskeleton. ..
- Cordenonsi M, D Atri F, Hammar E, Parry D, Kendrick Jones J, Shore D, et al. Cingulin contains globular and coiled-coil domains and interacts with ZO-1, ZO-2, ZO-3, and myosin. J Cell Biol. 1999;147:1569-82 pubmed..We propose that cingulin is a functionally important component of TJ, linking the submembrane plaque domain of TJ to the actomyosin cytoskeleton. ..
- Smalley K, Brafford P, Haass N, Brandner J, Brown E, Herlyn M. Up-regulated expression of zonula occludens protein-1 in human melanoma associates with N-cadherin and contributes to invasion and adhesion. Am J Pathol. 2005;166:1541-54 pubmed
- Elias B, Suzuki T, Seth A, Giorgianni F, Kale G, Shen L, et al. Phosphorylation of Tyr-398 and Tyr-402 in occludin prevents its interaction with ZO-1 and destabilizes its assembly at the tight junctions. J Biol Chem. 2009;284:1559-69 pubmed publisher..This study reveals a unique motif in the occludin sequence that is involved in the regulation of ZO-1 binding by reversible phosphorylation of specific Tyr residues. ..
- Willott E, Balda M, Fanning A, Jameson B, Van Itallie C, Anderson J. 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;90:7834-8 pubmed..The C-terminal domain of ZO-1, and its alternatively spliced region, appears to confer variable properties unique to tight junctions. ..
- Katsube T, Takahisa M, Ueda R, Hashimoto N, Kobayashi M, Togashi S. Cortactin associates with the cell-cell junction protein ZO-1 in both Drosophila and mouse. J Biol Chem. 1998;273:29672-7 pubmed..The potential roles of the cortactin.ZO-1 complex in cell adhesion and cell signaling are discussed. ..
- Schmidt A, Utepbergenov D, Krause G, Blasig I. Use of surface plasmon resonance for real-time analysis of the interaction of ZO-1 and occludin. Biochem Biophys Res Commun. 2001;288:1194-9 pubmed..We demonstrate the use of SPR spectroscopy as an effective approach for characterisation of the interactions of junction proteins. ..
- Zhong Y, Smart E, Weksler B, Couraud P, Hennig B, Toborek M. Caveolin-1 regulates human immunodeficiency virus-1 Tat-induced alterations of tight junction protein expression via modulation of the Ras signaling. J Neurosci. 2008;28:7788-96 pubmed publisher..Thus, caveolin-1 may provide an effective target to protect against Tat-induced HBMEC dysfunction and the disruption of the BBB in HIV-1-infected patients. ..
- Sallee J, Burridge K. Density-enhanced phosphatase 1 regulates phosphorylation of tight junction proteins and enhances barrier function of epithelial cells. J Biol Chem. 2009;284:14997-5006 pubmed publisher..These data suggest that DEP-1 can modify the phosphorylation state of tight junction proteins and play a role in regulating permeability. ..
- Willott E, Balda M, Heintzelman M, Jameson B, Anderson J. Localization and differential expression of two isoforms of the tight junction protein ZO-1. Am J Physiol. 1992;262:C1119-24 pubmed..These observations demonstrate the existence and variable expression of ZO-1 isoforms and raise the question whether these isoforms contribute to tight junction diversity in different epithelia...
- Rao R, Basuroy S, Rao V, Karnaky K, Gupta A. Tyrosine phosphorylation and dissociation of occludin-ZO-1 and E-cadherin-beta-catenin complexes from the cytoskeleton by oxidative stress. Biochem J. 2002;368:471-81 pubmed..These results show that oxidative stress induces tyrosine phosphorylation and cellular redistribution of occludin-ZO-1 and E-cadherin-beta-catenin complexes by a tyrosine-kinase-dependent mechanism. ..
- Bojarski C, Weiske J, Schoneberg T, Schröder W, Mankertz J, Schulzke J, et al. The specific fates of tight junction proteins in apoptotic epithelial cells. J Cell Sci. 2004;117:2097-107 pubmed..While the amount of claudin-2 protein was reduced similarly to occludin, ZO-1 and ZO-2, claudin-1 was either fully preserved or was even increased in apoptotic cells. ..
- Itoh M, Morita K, Tsukita S. Characterization of ZO-2 as a MAGUK family member associated with tight as well as adherens junctions with a binding affinity to occludin and alpha catenin. J Biol Chem. 1999;274:5981-6 pubmed..These findings indicated that ZO-2 forms a complex with ZO-1/occludin or ZO-1/alpha catenin to establish TJ or AJ domains, respectively. ..
- Giepmans B, Moolenaar W. The gap junction protein connexin43 interacts with the second PDZ domain of the zona occludens-1 protein. Curr Biol. 1998;8:931-4 pubmed..Confocal microscopy revealed that endogenous Cx43 and ZO-1 colocalised at gap junctions. We suggest that ZO-1 serves to recruit signalling proteins into Cx43-based gap junctions. ..
- Meerschaert K, Tun M, Remue E, De Ganck A, Boucherie C, Vanloo B, et al. The PDZ2 domain of zonula occludens-1 and -2 is a phosphoinositide binding domain. Cell Mol Life Sci. 2009;66:3951-66 pubmed publisher..This study shows for the first time that ZO isoforms bind PtdInsPs and offers an alternative regulatory mechanism for the formation and stabilisation of protein complexes in the nucleus. ..
- Wang T, Wang L, Moreno Vinasco L, Lang G, Siegler J, Mathew B, et al. Particulate matter air pollution disrupts endothelial cell barrier via calpain-mediated tight junction protein degradation. Part Fibre Toxicol. 2012;9:35 pubmed publisher..These findings support a novel mechanism for PM-induced lung damage and adverse cardiovascular outcomes. ..
- Itoh M, Nagafuchi A, Moroi S, Tsukita S. Involvement of ZO-1 in cadherin-based cell adhesion through its direct binding to alpha catenin and actin filaments. J Cell Biol. 1997;138:181-92 pubmed
- Haskins J, Gu L, Wittchen E, Hibbard J, Stevenson B. ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin. J Cell Biol. 1998;141:199-208 pubmed..In vitro affinity analyses demonstrated that recombinant 130-kD protein directly interacts with ZO-1 and the cytoplasmic domain of occludin, but not with ZO-2. We propose that this protein be named ZO-3. ..
- Nakamuta S, Endo H, Higashi Y, Kousaka A, Yamada H, Yano M, et al. Human immunodeficiency virus type 1 gp120-mediated disruption of tight junction proteins by induction of proteasome-mediated degradation of zonula occludens-1 and -2 in human brain microvascular endothelial cells. J Neurovirol. 2008;14:186-95 pubmed publisher..Our results demonstrate the novel molecular mechanisms of the BBB breakdown by gp120. ..
- Nielsen P, Baruch A, Shestopalov V, Giepmans B, Dunia I, Benedetti E, et al. Lens connexins alpha3Cx46 and alpha8Cx50 interact with zonula occludens protein-1 (ZO-1). Mol Biol Cell. 2003;14:2470-81 pubmed..The spatial variation in the interaction of ZO-1 with lens gap junctions is intriguing and is suggestive of multiple dynamic roles for this association. ..
- Nomme J, Fanning A, Caffrey M, Lye M, Anderson J, Lavie A. The Src homology 3 domain is required for junctional adhesion molecule binding to the third PDZ domain of the scaffolding protein ZO-1. J Biol Chem. 2011;286:43352-60 pubmed publisher..Our x-ray structures and NMR experiments also show for the first time a role for adjacent domains in the binding of ligands to PDZ domains in the MAGUK proteins family. ..
- Shen L, Weber C, Turner J. The tight junction protein complex undergoes rapid and continuous molecular remodeling at steady state. J Cell Biol. 2008;181:683-95 pubmed publisher..These data demonstrate that the tight junction undergoes constant remodeling and suggest that this dynamic behavior may contribute to tight junction assembly and regulation. ..
- Zhong Y, Zhang B, Eum S, Toborek M. HIV-1 Tat triggers nuclear localization of ZO-1 via Rho signaling and cAMP response element-binding protein activation. J Neurosci. 2012;32:143-50 pubmed publisher..The present results indicate the crucial role of Rho signaling and CREB in modulation of nuclear localization of ZO-1 and maintaining the integrity of endothelial monolayers. ..
- Wittchen E, Haskins J, Stevenson B. Protein interactions at the tight junction. Actin has multiple binding partners, and ZO-1 forms independent complexes with ZO-2 and ZO-3. J Biol Chem. 1999;274:35179-85 pubmed..ZO-3 complexes rather than a trimeric ZO-1.ZO-2.ZO-3 grouping. These studies elucidate direct binding interactions among tight junction-associated proteins, giving insight into their organization as a multimolecular structure. ..
- Hunter A, Gourdie R. The second PDZ domain of zonula occludens-1 is dispensable for targeting to connexin 43 gap junctions. Cell Commun Adhes. 2008;15:55-63 pubmed publisher..These data demonstrate that ZO-1 targets to GJ edges independently of several known PDZ2-mediated interactions, including ZO-1 homodimerization, heterodimerization with ZO-2, and direct ZO-1 binding to the C-terminal residues of Cx43. ..
- Li X, Ionescu A, Lynn B, Lu S, Kamasawa N, Morita M, et al. Connexin47, connexin29 and connexin32 co-expression in oligodendrocytes and Cx47 association with zonula occludens-1 (ZO-1) in mouse brain. Neuroscience. 2004;126:611-30 pubmed..Further, our findings suggest a scaffolding and/or regulatory role of ZO-1 at the oligodendrocyte side of astrocyte-to-oligodendrocyte gap junctions. ..
- Nielsen P, Beahm D, Giepmans B, Baruch A, Hall J, Kumar N. Molecular cloning, functional expression, and tissue distribution of a novel human gap junction-forming protein, connexin-31.9. Interaction with zona occludens protein-1. J Biol Chem. 2002;277:38272-83 pubmed..9 expression to vascular smooth muscle cells. Furthermore, it was demonstrated that Cx31.9 interacted with ZO-1. Thus, Cx31.9 represents a novel connexin gene that in vivo generates a protein with unique voltage gating properties. ..
- Sourisseau T, Georgiadis A, Tsapara A, Ali R, Pestell R, Matter K, et al. Regulation of PCNA and cyclin D1 expression and epithelial morphogenesis by the ZO-1-regulated transcription factor ZONAB/DbpA. Mol Cell Biol. 2006;26:2387-98 pubmed
- Raleigh D, Marchiando A, Zhang Y, Shen L, Sasaki H, Wang Y, et al. Tight junction-associated MARVEL proteins marveld3, tricellulin, and occludin have distinct but overlapping functions. Mol Biol Cell. 2010;21:1200-13 pubmed publisher..The data further suggest that these proteins are best considered as a group with both redundant and unique contributions to epithelial function and tight junction regulation. ..
- Moroi S, Saitou M, Fujimoto K, Sakakibara A, Furuse M, Yoshida O, et al. Occludin is concentrated at tight junctions of mouse/rat but not human/guinea pig Sertoli cells in testes. Am J Physiol. 1998;274:C1708-17 pubmed
- Itoh M, Nagafuchi A, Yonemura S, Kitani Yasuda T, 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;121:491-502 pubmed..Possible functions of the 220-kD protein (ZO-1) are discussed with special reference to the molecular mechanism for adherens and tight junction formation. ..
- Ibaraki H, Kanazawa T, Takashima Y, Okada H, Seta Y. Transdermal anti-nuclear kappaB siRNA therapy for atopic dermatitis using a combination of two kinds of functional oligopeptide. Int J Pharm. 2018;542:213-220 pubmed publisher..Thus, the combined treatment of STR-CH2R4H2C and AT1002 could serve as an effective transdermal siRNA therapeutic system for AD. ..
- Li R, Ning Z, Cui J, Yu F, Sioutas C, Hsiai T. Diesel exhaust particles modulate vascular endothelial cell permeability: implication of ZO-1 expression. Toxicol Lett. 2010;197:163-8 pubmed publisher..This increase in endothelium permeability is implicated in inflammatory cell transmigration into subendothelial layers with relevance to the initiation of atherosclerosis. ..
- Langan L, Harper G, Owen S, Purcell W, Jackson S, Jha A. Application of the rainbow trout derived intestinal cell line (RTgutGC) for ecotoxicological studies: molecular and cellular responses following exposure to copper. Ecotoxicology. 2017;: pubmed publisher..Overall, this model could be used to study the effects and predict aquatic gastrointestinal permeability of metals and other environmentally relevant contaminants in a cost effective and high throughput manner. ..
- Bender J, Engeholm M, Ederer M, Breu J, MÃ¸ller T, Michalakis S, et al. Corticotropin-Releasing Hormone Receptor Type 1 (CRHR1) Clustering with MAGUKs Is Mediated via Its C-Terminal PDZ Binding Motif. PLoS ONE. 2015;10:e0136768 pubmed publisher..The C-terminal PDZ (PSD-95, discs large, zona occludens 1) binding motif of CRHR1 is essential for its physical interaction with MAGUKs, as revealed by the CRHR1-STAVA ..
- Runkle E, Mu D. Tight junction proteins: from barrier to tumorigenesis. Cancer Lett. 2013;337:41-8 pubmed publisher..The focus of this review is to discuss the barrier function of the tight junction and to summarize the literature with a focus on the role of tight junction proteins in proliferation, transformation, and metastasis. ..
- Tzelepi V, Tsamandas A, Vlotinou H, Vagianos C, Scopa C. Tight junctions in thyroid carcinogenesis: diverse expression of claudin-1, claudin-4, claudin-7 and occludin in thyroid neoplasms. Mod Pathol. 2008;21:22-30 pubmed..A differential expression of tight junction proteins in the different histologic types of thyroid gland is noted. Additionally, claudin-1 expression may be an important prognostic indicator of recurrence in thyroid carcinomas. ..
- Song X, Zhao Y, Narcisse L, Duffy H, Kress Y, Lee S, et al. Canonical transient receptor potential channel 4 (TRPC4) co-localizes with the scaffolding protein ZO-1 in human fetal astrocytes in culture. Glia. 2005;49:418-29 pubmed..These data implicate TRPC4 in the regulation of calcium homeostasis in astrocytes, particularly as part of a signaling complex that forms at junctional sites between astrocytes. ..
- Nemeth Z, Szasz A, Somorácz A, Tátrai P, Nemeth J, Gyorffy H, et al. Zonula occludens-1, occludin, and E-cadherin protein expression in biliary tract cancers. Pathol Oncol Res. 2009;15:533-9 pubmed publisher..These results were confirmed by discriminant analysis yielding clear separation of the three normal sample groups from carcinomas in the corresponding locations. ..
- D Atri F, Nadalutti F, Citi S. Evidence for a functional interaction between cingulin and ZO-1 in cultured cells. J Biol Chem. 2002;277:27757-64 pubmed
- Cao G, Ye X, Xu Y, Yin M, Chen H, Kou J, et al. YiQiFuMai powder injection ameliorates blood-brain barrier dysfunction and brain edema after focal cerebral ischemia-reperfusion injury in mice. Drug Des Devel Ther. 2016;10:315-25 pubmed publisher..Our findings suggest that YQFM provides protection against focal cerebral I/R injury in mice, possibly by improving BBB dysfunction via upregulation of the expression of tight junction proteins. ..
- Chen Y, Statt S, Wu R, Chang H, Liao J, Wang C, et al. High mobility group box 1-induced epithelial mesenchymal transition in human airway epithelial cells. Sci Rep. 2016;6:18815 pubmed publisher..In conclusion, we found that HMGB1 induced EMT through RAGE and the PI3K/AKT/GSK3Î²/Î²-catenin signaling pathway. ..
- Tornavaca O, Chia M, Dufton N, Almagro L, Conway D, Randi A, et al. ZO-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation. J Cell Biol. 2015;208:821-38 pubmed publisher..ZO-1 is thus a central regulator of VE-cadherin-dependent endothelial junctions that orchestrates the spatial actomyosin organization, tuning cell-cell tension, migration, angiogenesis, and barrier formation. ..
- Neunlist M, Toumi F, Oreschkova T, Denis M, Leborgne J, Laboisse C, et al. Human ENS regulates the intestinal epithelial barrier permeability and a tight junction-associated protein ZO-1 via VIPergic pathways. Am J Physiol Gastrointest Liver Physiol. 2003;285:G1028-36 pubmed..In conclusion, our results strongly suggest a modulatory role of VIPergic submucosal neuronal pathways on intestinal epithelial barrier permeability and ZO-1 expression. ..
- Chen J, Pan L, Wei Z, Zhao Y, Zhang M. Domain-swapped dimerization of ZO-1 PDZ2 generates specific and regulatory connexin43-binding sites. EMBO J. 2008;27:2113-23 pubmed publisher..Therefore, our findings present a new paradigm for understanding how some PDZ domain proteins specifically bind to and regulate the functions of their target proteins. ..
- Polette M, Gilles C, Nawrocki Raby B, Lohi J, Hunziker W, Foidart J, et al. Membrane-type 1 matrix metalloproteinase expression is regulated by zonula occludens-1 in human breast cancer cells. Cancer Res. 2005;65:7691-8 pubmed..Such transfections concomitantly activated the beta-catenin/TCF/LEF pathway. Our results therefore show that ZO-1, besides its structural role in TJ assembly, can intervene in signaling events promoting tumor cell invasion. ..
- Aljameeli A, Thakkar A, Shah G. Calcitonin receptor increases invasion of prostate cancer cells by recruiting zonula occludens-1 and promoting PKA-mediated TJ disassembly. Cell Signal. 2017;36:1-13 pubmed publisher..In brief, the present study identifies the significance of CTR-ZO-1 interaction in progression of prostate cancer to its metastatic form. ..
- Qian Y, Li C, Jiang A, Ge S, Gu P, Fan X, et al. HIV-1 gp120 Glycoprotein Interacting with Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Non-integrin (DC-SIGN) Down-Regulates Tight Junction Proteins to Disrupt the Blood Retinal Barrier and Increase Its Permeability. J Biol Chem. 2016;291:22977-22987 pubmed..This study elucidates a novel mechanism by which HIV, type 1 invades ocular tissues and provides additional insights into the translocation or invasion process of ocular complication-associated pathogens. ..
- Kizhatil K, Bennett V. Lateral membrane biogenesis in human bronchial epithelial cells requires 190-kDa ankyrin-G. J Biol Chem. 2004;279:16706-14 pubmed..These results demonstrate that 190-kDa ankyrin-G plays a pleiotropic role in assembly of lateral membranes of bronchial epithelial cells. ..
- Goler Baron V, Sladkevich I, Assaraf Y. Inhibition of the PI3K-Akt signaling pathway disrupts ABCG2-rich extracellular vesicles and overcomes multidrug resistance in breast cancer cells. Biochem Pharmacol. 2012;83:1340-8 pubmed publisher..We propose that Akt signaling inhibitors which disrupt ABCG2 targeting and EVs biogenesis may readily overcome MDR thus warranting in vivo studies with these promising drug combinations...
- Jurkiewicz D, Michalec K, Skowronek K, Nałęcz K. Tight junction protein ZO-1 controls organic cation/carnitine transporter OCTN2 (SLC22A5) in a protein kinase C-dependent way. Biochim Biophys Acta Mol Cell Res. 2017;1864:797-805 pubmed publisher..It is postulated that ZO-1, when not phosphorylated by PKC, keeps Octn2 in an active state, while elimination of this binding in ?PDZ mutant or after ZO-1 phosphorylation leads to diminution of Octn2 activity. ..
- Hirakawa H, Shibata K, Nakayama T. Localization of cortactin is associated with colorectal cancer development. Int J Oncol. 2009;35:1271-6 pubmed..We conclude that localization of cortactin in cancer cells and interaction between ZO-1 and cortactin are crucial for cancer progression. ..
- Stiffler M, Grantcharova V, Sevecka M, MacBeath G. Uncovering quantitative protein interaction networks for mouse PDZ domains using protein microarrays. J Am Chem Soc. 2006;128:5913-22 pubmed
- Hanajima Ozawa M, Matsuzawa T, Fukui A, Kamitani S, Ohnishi H, Abe A, et al. Enteropathogenic Escherichia coli, Shigella flexneri, and Listeria monocytogenes recruit a junctional protein, zonula occludens-1, to actin tails and pedestals. Infect Immun. 2007;75:565-73 pubmed..We propose that an analysis of the recruitment on a molecular basis will lead to an understanding of how ZO-1 recognizes a distinctive actin-rich structure under pathophysiological conditions. ..
- Mahajan S, Aalinkeel R, Sykes D, Reynolds J, Bindukumar B, Fernandez S, et al. Tight junction regulation by morphine and HIV-1 tat modulates blood-brain barrier permeability. J Clin Immunol. 2008;28:528-41 pubmed publisher..These studies may lead to the development of novel anti-HIV-1 therapeutics that target specific TJ proteins, thus preventing TJ disruption in opiate using HIV-1 patients. ..
- Mellas R, Leigh N, Nelson J, McCall A, Baker O. Zonula occludens-1, occludin and E-cadherin expression and organization in salivary glands with Sjögren's syndrome. J Histochem Cytochem. 2015;63:45-56 pubmed publisher..Our results suggest that ZO-1, occludin and E-cadherin are not altered in areas without lymphocytic infiltration. However, future studies will be necessary to test the functional aspect of these results. ..
- Cohen C, Shieh J, Pickles R, Okegawa T, Hsieh J, Bergelson J. The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction. Proc Natl Acad Sci U S A. 2001;98:15191-6 pubmed..These results indicate that CAR is a component of the tight junction and of the functional barrier to paracellular solute movement. Sequestration of CAR in tight junctions may limit virus infection across epithelial surfaces. ..
- Ban Y, Dota A, Cooper L, Fullwood N, Nakamura T, Tsuzuki M, et al. Tight junction-related protein expression and distribution in human corneal epithelium. Exp Eye Res. 2003;76:663-9 pubmed..Not only occludin, but also some claudins act as integral transmembrane proteins in the corneal epithelium. ZO-1 is a component of the corneal epithelial tight junction, as it is in most epithelial cells. ..
- Kang H, Wang C, Dou L, Qing Y, Han X, Sun J, et al. [Methylation status of ZO-1 gene in patients with myelodysplastic syndrome]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008;16:70-3 pubmed..The ZO-1 gene may be a potential gene related to hematologic malignancies. ..