Affinage

TJP1

Tight junction protein 1 · UniProt Q07157

Length
1748 aa
Mass
195.5 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TJP1 (ZO-1) is a multidomain scaffolding protein that organizes epithelial and endothelial cell-cell junctions and couples junction assembly to cytoskeletal mechanics, gene expression, and cell proliferation (PMID:16923393, PMID:29199076). At tight junctions, ZO-1 and its paralog ZO-2 dictate where claudins are polymerized into strands, a function that requires ZO-1's non-PDZ C-terminal regions rather than its PDZ1-3 cassette alone (PMID:16923393); ZO-1 loss markedly retards junction formation and reduces cingulin recruitment without abolishing steady-state junctions, defining non-redundant roles (PMID:15292177). ZO-1 behaves as a mechanosensor: it forms liquid-liquid phase-separated cytoplasmic condensates that are carried to junctions by actomyosin-driven retrograde flow through direct actin binding (PMID:31675500, PMID:35198899), and it switches between folded (autoinhibited) and stretched conformations under tensile force (2-20 pN), the stretched state exposing the ZPSG region to recruit the Y-box transcription factor DbpA/ZONAB and occludin (PMID:29199076). Through SH3-domain binding, ZO-1 sequesters ZONAB and its partner CDK4 at junctions to lower their nuclear levels and suppress proliferation in a cell-density-dependent manner (PMID:10790369, PMID:12566432). ZO-1 also governs actomyosin organization and small-GTPase signaling, driving Rac1-dependent maturation of belt-like adherens junctions and RhoA/ROCK-dependent integration of myosin-2 into the zonula adherens (PMID:17353356, PMID:18596233), and in endothelium it tunes tension on VE-cadherin by recruiting JACOP/p114RhoGEF, thereby controlling barrier function and angiogenesis (PMID:25753039). Beyond junction scaffolding, ZO-1 binds connexin-43 via its second PDZ domain and regulates gap junction plaque assembly, channel turnover, and phosphorylation-gated disengagement and endocytosis of Cx43 (PMID:12064592, PMID:29021339). ZO-1 associates with centrioles and mitotic spindle poles to orient spindles for epithelial repair (PMID:34478742), and its cingulin interaction through the ZU5 domain stabilizes the extended conformation and TJ accumulation (PMID:35259394). In vivo conditional deletion establishes ZO-1 as indispensable for the podocyte filtration barrier (PMID:25184792), AV-node conduction via gap junction protein localization (PMID:32347164), apical surface assembly (PMID:30242130), and mucosal repair (PMID:34478742). ZO-1 additionally moonlights in cytoplasmic regulatory circuits, restraining PER1 nuclear entry to modulate the hepatic circadian clock under mTOR control (PMID:32001717) and binding YB-1 to suppress stress granule formation during angiogenesis (PMID:38782923).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 High

    Established that ZO-1 is not merely a structural scaffold but links junction occupancy to transcription by binding a Y-box factor.

    Evidence Co-IP, reporter assay and stable overexpression mapping ZONAB binding to the ZO-1 SH3 domain and regulation of ErbB-2 promoter

    PMID:10790369

    Open questions at the time
    • Did not establish the proliferation consequence
    • Mechanism of density-dependent shuttling unresolved
  2. 2003 High

    Showed ZO-1 actively suppresses proliferation by sequestering ZONAB and CDK4 at junctions, connecting junction integrity to cell-cycle control.

    Evidence ZONAB knockdown, ZO-1 overexpression, nuclear fractionation and ZONAB/CDK4 co-IP in epithelial cells

    PMID:12566432

    Open questions at the time
    • Did not define how tension or junction state triggers ZONAB release
    • CDK4 binding to ZONAB not structurally mapped
  3. 2004 High

    Distinguished ZO-1 from ZO-2 functionally, showing ZO-1 is specifically required for the rate of TJ assembly and cingulin recruitment.

    Evidence ZO-1 KO epithelial cells, calcium-switch assay, TER and rescue with ZO-1 vs ZO-2

    PMID:15292177

    Open questions at the time
    • Mechanism of cingulin recruitment defect not defined here
    • Why ZO-2 cannot substitute unclear at this stage
  4. 2006 High

    Resolved which ZO-1 regions drive claudin strand formation, demonstrating non-PDZ domains are essential for polymerization.

    Evidence ZO-1/ZO-2 double-deficient cells with truncation-mutant rescue and forced membrane recruitment, immunofluorescence

    PMID:16923393

    Open questions at the time
    • The biophysical basis of claudin polymerization by non-PDZ regions not defined
    • No structural model of the strand-organizing interaction
  5. 2007 High

    Extended ZO-1 function to adherens junction maturation via Rac1, linking the scaffold to small-GTPase signaling.

    Evidence ZO-1/ZO-2 double-deficient cells, Rac1 activity assay and ZO-1 deletion mutants

    PMID:17353356

    Open questions at the time
    • How ZO-1 activates Rac1 mechanistically not defined
    • Direct GEF link not identified
  6. 2008 High

    Showed ZO-1/ZO-2 drive myosin-2 integration into the zonula adherens through RhoA/ROCK, defining a contractility-organizing role.

    Evidence Domain-deletion rescue, FRET Rho activation assay, RhoA/ROCK perturbation in double-deficient cells

    PMID:18596233

    Open questions at the time
    • RhoA activation mechanism by ZO-1 not identified here
    • ROCK shown necessary but not sufficient
  7. 2015 High

    Defined the endothelial-specific mechanism: ZO-1 sets VE-cadherin tension via JACOP/p114RhoGEF, controlling barrier and angiogenesis.

    Evidence siRNA depletion, VE-cadherin FRET tension sensor, co-IP and in vivo/in vitro angiogenesis assays

    PMID:25753039

    Open questions at the time
    • Direct vs indirect JACOP recruitment not fully resolved
    • Generalizability to epithelial junctions untested here
  8. 2017 High

    Revealed the force-dependent conformational switch in ZO-1 that mechanically gates DbpA/occludin recruitment.

    Evidence Magnetic tweezers single-molecule force, SIM, PLA and pull-downs with ZPSG/C-terminal domain mutants

    PMID:29199076

    Open questions at the time
    • In vivo tension thresholds not directly measured
    • Coupling to ZONAB/CDK4 nuclear shuttling not closed
  9. 2017 Medium

    Mapped Cx43 phosphosite control of ZO-1 binding, showing ZO-1 disengagement gates gap junction channel closure and turnover.

    Evidence Systematic phosphomimetic/dead Cx43 mutants, co-IF, clathrin binding and half-life assays

    PMID:29021339

    Open questions at the time
    • Kinase-substrate causality inferred from mutants, not in situ
    • Single-lab data
  10. 2019 High

    Established that ZO-1 acts through liquid-liquid phase separation and actomyosin-driven flow, conferring tight-junction mechanosensitivity.

    Evidence Live imaging in zebrafish embryo, laser ablation, FRAP, actin-binding mutants and actomyosin perturbation

    PMID:31675500

    Open questions at the time
    • Molecular determinants of condensate formation not fully defined
    • Relationship to the stretch/fold switch not integrated
  11. 2021 High

    Uncovered a non-junctional role: ZO-1 at centrioles/spindle poles orients mitotic spindles for mucosal repair.

    Evidence Intestinal conditional Tjp1 KO mice, colitis models, colonoids, spindle/centriole imaging

    PMID:34478742

    Open questions at the time
    • How ZO-1 localizes to centrioles unknown
    • Spindle-orientation partners at the pole not identified
  12. 2022 High

    Defined the cingulin-ZU5 interaction that stabilizes the extended ZO-1 conformation and TJ accumulation.

    Evidence GST pull-downs, KO cells, SIM, FRAP and in vitro DbpA binding

    PMID:35259394

    Open questions at the time
    • How cingulin biases the conformational equilibrium mechanistically unclear
    • Integration with tension-driven stretching not closed
  13. 2022 Medium

    Separated tension-dependent from tension-independent ZO-1 functions in TJ architecture using tunable ECM stiffness.

    Evidence ZO-1 KO cells on tunable substrates, FRET tension sensors, actomyosin inhibition rescue

    PMID:36497035

    Open questions at the time
    • Molecular basis of tension-independent architecture defect unknown
    • Single-lab data
  14. 2024 Medium

    Identified a YB-1/stress-granule axis through which ZO-1 supports endothelial angiogenesis beyond junction scaffolding.

    Evidence ZO-1 interactome MS, co-IP, siRNA, endothelial-specific KO mouse and retinal vasculature imaging

    PMID:38782923

    Open questions at the time
    • Whether junctional or cytoplasmic ZO-1 pools mediate this not resolved
    • Direct vs indirect YB-1 binding interface not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ZO-1's distinct activities — claudin polymerization, the force-gated stretch/fold switch, phase separation, GTPase control, and cytoplasmic moonlighting (PER1, YB-1) — are coordinated within a single molecule and partitioned between junctional and non-junctional pools remains unresolved.
  • No integrated structural model linking conformation, LLPS and actin binding
  • Pool-specific (junctional vs cytoplasmic) regulation of moonlighting functions undefined
  • In vivo significance of circadian and stress-granule roles relative to barrier function unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3 GO:0140313 molecular sequestering activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 3 GO:0005634 nucleus 2 GO:0005856 cytoskeleton 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1500931 Cell-Cell communication 4 R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
CDK4CJN/CINGULINCLDN16GJA1/CX43OCLN/OCCLUDINPER1YBX1ZONAB/DBPA
Complex memberships
gap junction plaquetight junctionzonula adherens

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 ZO-1 and ZO-2 independently determine where claudins are polymerized during tight junction strand formation. In ZO-1/ZO-2 double-deficient epithelial cells, tight junctions are completely absent. When exogenous ZO-1 or ZO-2 is expressed, claudins are polymerized at junctional areas. A truncated ZO-1 containing only PDZ1-3 domains fails to support claudin polymerization unless forcibly recruited to lateral membranes and dimerized, demonstrating that ZO-1's non-PDZ regions are required for proper localization and claudin polymerization. Homologous recombination KO + RNAi double-depletion, exogenous rescue with truncation mutants, immunofluorescence Cell High 16923393
2000 ZO-1 binds through its SH3 domain to the Y-box transcription factor ZONAB (ZO-1-associated nucleic acid-binding protein). ZONAB localizes to both the nucleus and tight junctions, and together ZO-1 and ZONAB regulate ErbB-2 promoter activity in a cell density-dependent manner, linking tight junction occupancy to gene expression control. Co-immunoprecipitation, reporter assay, stable overexpression, immunofluorescence The EMBO journal High 10790369
2003 ZO-1 sequesters the transcription factor ZONAB at tight junctions, reducing nuclear ZONAB levels and nuclear CDK4, thereby suppressing epithelial cell proliferation and limiting cell density. ZONAB associates with CDK4, and overexpression of ZO-1 or ZO-1 fragments that bind ZONAB reduces nuclear CDK4 accumulation. Antisense/RNAi knockdown of ZONAB, overexpression of ZO-1, nuclear fractionation, co-immunoprecipitation of ZONAB/CDK4 The Journal of cell biology High 12566432
2019 ZO-1 undergoes liquid-liquid phase separation to form non-junctional cytoplasmic clusters. Actomyosin tension drives retrograde flow that transports these ZO-1 clusters to tight junctions, where direct actin binding of ZO-1 is required for stable incorporation. This phase-separation-and-flow mechanism confers mechanosensitivity to tight junctions in the zebrafish gastrulating embryo. Live imaging in zebrafish embryo, laser ablation, FRAP, actin-binding domain mutants, pharmacological perturbation of actomyosin Cell High 31675500
2017 ZO-1 exists in stretched and folded conformations depending on actomyosin-generated tension. Intramolecular interactions between N-terminal ZPSG and C-terminal domains of ZO-1 prevent binding of DbpA (ZONAB) to the ZPSG in the folded state; tensile force (2–20 pN) disrupts this autoinhibition to allow stretched ZO-1 to recruit DbpA and occludin to junctions, controlling gene expression, proliferation, barrier function, and cyst morphogenesis. Structured illumination microscopy, proximity ligation assay, pull-down with domain mutants, magnetic tweezers single-molecule experiments, actomyosin inhibition Current biology : CB High 29199076
2004 ZO-1 knockout epithelial cells (ZO-1−/−) form well-organized tight junctions at confluency but exhibit markedly retarded tight junction formation (claudin/occludin recruitment and barrier establishment) during calcium-switch polarization. ZO-1 deficiency also reduced cingulin recruitment to tight junctions and increased ZO-2 recruitment; both cingulin loss and retarded TJ formation were rescued by exogenous ZO-1 but not ZO-2, indicating non-redundant roles. Homologous recombination KO, calcium-switch assay, transepithelial resistance, immunofluorescence, rescue by exogenous expression The Journal of biological chemistry High 15292177
2007 ZO-1 is required for conversion of primordial 'fibroblastic' adherens junctions to belt-like polarized epithelial adherens junctions during epithelial polarization, acting via Rac1 activation. ZO-1/ZO-2-deficient cells show severely impaired Rac1 activation upon primordial AJ formation. Mutational analysis shows that distinct ZO-1 domains are required for belt-like AJ formation versus TJ formation. ZO-1/ZO-2 double-deficient cells, Rac1 activity assay, ZO-1 deletion mutants, immunofluorescence The Journal of cell biology High 17353356
2008 ZO-1 and ZO-2 are required for integration of myosin-2 into the zonula adherens. In ZO-1/ZO-2-deficient cells, linearized but fragmented adherens junctions lacking myosin-2 (pre-zonula AJ) form. Full-length ZO-1 or ZO-2 lacking PDZ1/2 but not PDZ1/2/3 restores myosin-2 integration. ZO-1/2-dependent RhoA activation (requiring ROCK as necessary but not sufficient) mediates myosin-2 junctional integration. ZO-1/ZO-2 double-deficient cells, domain deletion rescue, RhoA/ROCK manipulation, FRET-based Rho activation assay, immunofluorescence Molecular biology of the cell High 18596233
2015 ZO-1 controls endothelial adherens junctions by regulating tension on VE-cadherin. ZO-1 depletion redistributes active myosin II from junctions to stress fibers, reduces tension on VE-cadherin, and causes loss of junctional mechanotransducers (vinculin, PAK2). ZO-1 is required for junctional recruitment of JACOP, which in turn recruits p114RhoGEF, linking ZO-1 to actomyosin spatial organization, cell-cell tension, migration, angiogenesis, and barrier function. siRNA depletion, ROCK inhibition rescue, FRET tension sensor on VE-cadherin, co-immunoprecipitation, in vitro and in vivo angiogenesis assays The Journal of cell biology High 25753039
2001 The second PDZ domain of ZO-1, but not the first, directly binds to the C-terminus of connexin-43 (Cx43), and the very C-terminal isoleucine residue of Cx43 is critical for this interaction. GST pull-down with PDZ domain fragments, mutagenesis of Cx43 C-terminus Cell communication & adhesion Medium 12064592
2005 ZO-1 regulates Cx43-mediated gap junction formation and function in osteoblastic cells. Disruption of the Cx43/ZO-1 interaction by a dominant-negative ZO-1 fragment decreased dye transfer by 85% and redistributed Cx43 into lipid raft fractions. Conversely, ZO-1 overexpression increased gap junctional permeability and appositional Cx43. ZO-1-mediated delivery of Cx43 from lipid rafts to gap junctional plaques is proposed as a regulatory step in gap junction formation. Dominant-negative ZO-1 expression, surface biotinylation, sucrose gradient fractionation, dye transfer assay Journal of cell science Medium 15855237
2006 ZO-1 is required for PKC-γ-driven disassembly of Cx43 from gap junction plaques. siRNA knockdown of ZO-1 caused stable interaction of PKC-γ with Cx43 in the absence of activation, and upon TPA-induced PKC-γ activation, Cx43 failed to disassemble from plaques despite S368 phosphorylation, indicating ZO-1 is required downstream of phosphorylation for gap junction remodeling. siRNA knockdown, co-immunoprecipitation, confocal microscopy, dye transfer assay Cellular signalling Medium 17210245
2017 Phosphorylation of Cx43 at S365, S368, and S373 (Akt, PKA, PKC sites) regulates ZO-1 binding and release. Phosphomimetic or phosphorylation-dead mutations at these sites cause ZO-1 to bind throughout gap junction plaques rather than only at their periphery, or abolish binding entirely (S373E). Inability to disengage from ZO-1 correlates with increased plaque size, longer connexin half-life, and retention of open functional channels, indicating ZO-1 disengagement is required for channel closure and endocytosis. Phosphomimetic and phosphorylation-dead Cx43 mutants expressed in HeLa and MDCK cells, co-immunofluorescence, clathrin binding assay, Western blot for protein half-life Molecular biology of the cell Medium 29021339
2016 ZO-1 is necessary for single lumen formation in 3D epithelial cysts. The actin-binding region (ABR) and U5-GuK domain of ZO-1 are required for this function. Among U5-GuK binding partners (shroom2, α-catenin, occludin), only occludin deletion phenocopies ZO-1 loss (multi-lumen cysts, mitotic spindle orientation defects). The ZO-1–occludin interaction through the occludin OCEL domain is required for single lumen development. ZO-1 KO cells, domain deletion mutants, 3D cyst assay, occludin KO rescue, mitotic spindle analysis Journal of cell science High 27802160
2018 ZO-1 U5 and GuK domains are necessary for proper apical surface assembly (microvilli organization, cortical F-actin) in vivo and in vitro. PDZ1 deletion rescues apical structure in ZO-1-deficient cells but not in ZO-1/ZO-2 double-deficient cells, indicating heterodimerization with ZO-2 restores PDZ1-dependent interactions. Pharmacological F-actin disruption, myosin II inhibition, or dynamin inactivation rescue apical structure in ZO-1 KO, indicating ZO-1 directs epithelial organization by regulating actomyosin contraction and membrane traffic. Intestinal epithelial-specific KO mouse, domain deletion mutants, pharmacological inhibitors, immunofluorescence, electron microscopy The Journal of biological chemistry High 30242130
2021 ZO-1 is dispensable for steady-state intestinal barrier function in vivo but is critical for mucosal repair. ZO-1-deficient intestinal epithelium fails to upregulate proliferation in response to Wnt signaling in vitro and damage in vivo. ZO-1 associates with centrioles in interphase cells and mitotic spindle poles during division; in its absence, mitotic spindles fail to orient correctly, causing mitotic catastrophe. Intestinal epithelial-specific Tjp1 conditional KO mouse, colitis models, colonoid cultures, mitotic spindle imaging, immunofluorescence with spindle/centriole markers Gastroenterology High 34478742
2001 ZO-1 is recruited to nectin-based cell-cell adhesion sites through afadin, independently of α-catenin. Using cadherin-deficient and α-catenin-deficient cell lines expressing components of the nectin-afadin and cadherin-catenin systems, nectin recruits ZO-1 via afadin but not via ponsin or α-catenin. Cadherin-deficient and α-catenin-deficient cell lines with stable expression of individual components, immunofluorescence co-localization Molecular biology of the cell Medium 11408571
1999 AF-6 interacts with activated Ras and ZO-1 in vivo. Endogenous AF-6 is co-immunoprecipitated with activated Ras from cells expressing activated Ras, and AF-6 is co-immunoprecipitated with ZO-1 from Rat1 cells. A single amino acid mutation in the N-terminal RA domain of AF-6 abolishes interaction with activated Ras. Co-immunoprecipitation from mammalian cells, RA domain point mutation, c-fos reporter assay Biochemical and biophysical research communications Medium 10334923
2002 Cingulin binds to ZO-1 via a conserved ZO-1 interaction motif (ZIM) at the N-terminus of cingulin; this ZIM is required for cingulin-ZO-1 interaction in vitro and for cingulin recruitment to ZO-1-containing adherens junctions in fibroblasts. Overexpression of Xenopus cingulin in A6 cells disrupts endogenous ZO-1 localization, demonstrating a functional interaction. GST pull-down, transfection with ZIM deletion mutants, immunofluorescence in A6 and Rat-1 cells The Journal of biological chemistry Medium 12023291
2022 Cingulin binds to the C-terminal ZU5 domain of ZO-1. This interaction promotes the extended (stretched) conformation of ZO-1 and is required for ZO-1 stabilization and accumulation at tight junctions. KO of cingulin decreases ZO-1 at TJs; ZO-1 lacking the ZU5 domain has a folded conformation, higher mobile fraction by FRAP, and reduced TJ accumulation. GST pull-downs, KO cells, structured illumination microscopy, FRAP, immunofluorescence, in vitro DbpA binding assay The Journal of biological chemistry High 35259394
2004 The C-terminal TRV sequence of paracellin-1 (PCLN-1/claudin-16) directly interacts with ZO-1. Mutations abolishing the PCLN-1/ZO-1 association prevent proper tight junction localization of PCLN-1 and reduce paracellular Ca2+ transport, demonstrating that ZO-1 interaction is required for PCLN-1 TJ targeting and divalent cation reabsorption. GST fusion protein pull-down, co-immunoprecipitation, stable expression of PCLN-1 mutants in MDCK cells, 45Ca2+ flux assay The Journal of biological chemistry Medium 15496416
2010 ZO-1 determines the localization of adherens junctions (N-cadherin) and gap junctions (Cx43) at cardiac intercalated disks. Expression of a dominant-negative ZO-1 construct reduces ZO-1–N-cadherin interaction and causes cytoplasmic internalization of both AJ and GJ proteins, as well as breakdown of the normal ICD pattern of small interior and large peripheral gap junctions. Dominant-negative ZO-1 construct in rat ventricular myocytes in vitro and in vivo, co-immunoprecipitation, immunofluorescence American journal of physiology. Heart and circulatory physiology Medium 21131473
2020 Cardiomyocyte-specific deletion of ZO-1 (Tjp1) causes atrioventricular (AV) block without affecting heart rate. Conduction system-specific deletion in the AV node (Hcn4-Cre) also causes AV block, whereas deletion distal to the AV node (Kcne1-Cre) does not. ZO-1 loss in the AV node decreases Cx40 expression and intercalated disc localization, demonstrating that ZO-1 maintains AV node conduction by preserving gap junction protein localization. Inducible cardiomyocyte-specific and conduction system-specific Tjp1 conditional KO mice, ECG, ex vivo optical mapping, immunostaining, Western blot Circulation research High 32347164
2008 ZO-1 knockdown inhibits morula-to-blastocyst transformation in mouse embryos. ZO-1 siRNA delivery reduces ZO-1 protein, prevents fluid accumulation and blastocoel formation, and reduces expression of trophoblast markers Cdx2 and Oct-4, without affecting ZO-2 or F-actin, establishing a ZO-1-specific role in blastocyst formation. Electroporation-based siRNA delivery in mouse embryos, morphological assessment, Western blot, immunofluorescence Developmental biology Medium 18423437
2014 Podocyte-specific deletion of Tjp1/ZO-1 downregulates podocyte membrane protein expression, impairs foot process interdigitation and slit diaphragm formation, and results in proteinuria and glomerular sclerosis, demonstrating that ZO-1 is indispensable for the podocyte filtration barrier. Podocyte-specific conditional Tjp1 KO mouse, histology, electron microscopy, urinalysis, immunofluorescence PloS one High 25184792
2019 An alternative TJP1 isoform lacking exon 20 (encoding the α-domain; TJP1-α−) is generated during TGF-β-induced EMT, regulated by the splicing factor RBM47. The TJP1-α− isoform enhances actin stress fiber assembly and promotes cell migration in wound healing assays. RBM47 promotes exon 20 inclusion via binding (U)GCAUG in the downstream intronic region through its first RRM domain. Alternative splicing analysis, RBM47 KD/OE, wound healing assay, actin staining, luciferase splice reporter Oncogene Medium 31358901
2022 ZO-1 forms cytoplasmic condensates via liquid-liquid phase separation in early mouse trophectoderm. These condensates dissolve and ZO-1 accumulates at cell junctions as blastocyst cavity pressure increases. The dynamics of ZO-1 condensate dissolution depend on physical tension mediated through ZO-1–F-actin interaction, as shown in MDCK cells. Live imaging in mouse embryos, MDCK cell LLPS assay, FRAP, actin interaction mutants iScience Medium 35198899
2020 TJP1/ZO-1 functions as a mediator of mTOR signaling to modulate the hepatic circadian clock. ZO-1 interacts with PER1 and prevents its nuclear translocation. During feeding, mTOR phosphorylates ZO-1, which attenuates the ZO-1–PER1 association, thereby allowing PER1 nuclear shuttling to dampen circadian oscillation. Co-immunoprecipitation of ZO-1 and PER1, mTOR inhibition, ZO-1 KD, nuclear/cytoplasmic fractionation, circadian reporter assays Nature communications Medium 32001717
2024 BHB (beta-hydroxybutyrate), taken up via MCT1 in cerebral endothelium, upregulates ZO-1 expression by enhancing β-hydroxybutyrylation of H3K9 at the TJP1 gene promoter, thereby restoring blood-brain barrier integrity after ischemic stroke. In vivo stroke model with BHB supplementation, shRNA targeting HMGCS2, ChIP for H3K9 β-hydroxybutyrylation at TJP1 promoter, microvascular ZO-1 conditional KO mice Advanced science Medium 38666466
2024 ZO-1 interacts with the RNA-binding protein YB-1, a component of stress granules (SGs). Downregulation of ZO-1 increases SG formation in response to stress, and stress (arsenite) decreases ZO-1–YB-1 interaction to drive SG assembly. Endothelial-specific ZO-1 deletion in mice increases YB-1-positive granules in retinal endothelial cells, alters tip cell morphology, and arrests retinal vascular expansion. ZO-1 interactome by MS, co-IP of ZO-1 and YB-1, siRNA KD, endothelial-specific KO mouse, retinal vasculature imaging Nature communications Medium 38782923
2022 ZO-1 depletion disrupts tight junction assembly and epithelial morphogenesis in an ECM stiffness-dependent manner. ZO-1 depletion reorganizes active myosin in a stiffness-dependent way, and junction formation and morphogenesis are rescued by inhibition of actomyosin contractility. However, even at low tension, ZO-1 KO cells assemble functional barriers but with structurally abnormal tight junctions (reduced and discontinuous junctional components), revealing tension-independent ZO-1 functions in TJ architecture. ZO-1 KO cells, tunable ECM stiffness substrates, FRET tension sensors at cell-matrix and E-cadherin adhesions, actomyosin inhibition, immunofluorescence Cells Medium 36497035
2017 ZO-1 binds to α5β1 integrin, and this complex decreases the resistance to force of α5β1-fibronectin adhesions at the edge of migrating cell monolayers while increasing α5β1 recruitment, consistent with a molecular clutch model. Disrupting the ZO-1/α5β1 complex reduces adhesion density and intensity at the migration edge. Co-immunoprecipitation, magnetic tweezers force measurements on α5β1-fibronectin links, migration assays, quantification of adhesion density Molecular biology of the cell Medium 28251923
2011 In Drosophila, the ZO-1 homologue Polychaetoid (Pyd) acts together with Canoe (Afadin homologue) and Enabled to regulate actin cytoskeleton anchoring/regulation during dorsal closure. Loss of Pyd and Canoe together causes early junction failure particularly at multicellular junctions. Pyd and Cno are required for proper Enabled localization during dorsal closure. Pyd null alleles in Drosophila, genetic epistasis with canoe and enabled mutants, live imaging, immunofluorescence Molecular biology of the cell Medium 21508316
2010 ZO-1 co-localizes with WTIP in cultured mouse podocyte adherens junctions. Upon puromycin aminonucleoside injury, ZO-1 (together with WTIP) translocates from podocyte adherens junctions to the nucleus, correlating with increased albumin flux and reduced WT1 target gene expression. Immunofluorescence co-localization, nuclear/cytoplasmic fractionation, albumin flux assay American journal of physiology. Renal physiology Low 15798086
2010 ZO-1 physically interacts with Cx43 in human trophoblastic cells (demonstrated by co-immunoprecipitation). siRNA knockdown of ZO-1 reduces trophoblast cell-cell fusion and Cx43 expression, demonstrating a functional role for ZO-1 in trophoblast differentiation. Co-immunoprecipitation, siRNA KD, gap-FRAP measurement of gap junction communication, fusion index quantification American journal of physiology. Cell physiology Medium 20200207
2023 TJP1/ZO-1 knockdown in human pluripotent stem cells allows BMP4 to robustly and ubiquitously activate pSMAD1/5 signaling, disrupting gastrulation-associated patterning and causing differentiation bias toward primordial germ cell-like cells, demonstrating that ZO-1 regulates spatial BMP4 signaling and gastrulation patterning by restricting pSMAD1/5 activation. TJP1 siRNA KD in hPSC gastruloid model, pSMAD1/5 immunofluorescence, flow cytometry for PGCLC markers Developmental cell Medium 37354899

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 ZO-1 and ZO-2 independently determine where claudins are polymerized in tight-junction strand formation. Cell 661 16923393
2015 ZO-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation. The Journal of cell biology 455 25753039
2022 Tight junction proteins occludin and ZO-1 as regulators of epithelial proliferation and survival. Annals of the New York Academy of Sciences 438 35580994
2021 The Tight Junction Protein ZO-1 Is Dispensable for Barrier Function but Critical for Effective Mucosal Repair. Gastroenterology 401 34478742
2004 Toll-like receptor 2 enhances ZO-1-associated intestinal epithelial barrier integrity via protein kinase C. Gastroenterology 374 15236188
2000 The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression. The EMBO journal 352 10790369
2003 The ZO-1-associated Y-box factor ZONAB regulates epithelial cell proliferation and cell density. The Journal of cell biology 311 12566432
1990 The tight junction protein ZO-1 is concentrated along slit diaphragms of the glomerular epithelium. The Journal of cell biology 259 2202736
2004 Establishment and characterization of cultured epithelial cells lacking expression of ZO-1. The Journal of biological chemistry 223 15292177
2019 Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow. Cell 185 31675500
2007 Requirement of ZO-1 for the formation of belt-like adherens junctions during epithelial cell polarization. The Journal of cell biology 155 17353356
2001 Connexin-43 interactions with ZO-1 and alpha- and beta-tubulin. Cell communication & adhesion 134 12064592
2017 Tension-Dependent Stretching Activates ZO-1 to Control the Junctional Localization of Its Interactors. Current biology : CB 121 29199076
2005 Roles of ZO-1, occludin, and actin in oxidant-induced barrier disruption. American journal of physiology. Gastrointestinal and liver physiology 120 16239402
2000 Tight junction proteins ZO-1, ZO-2, and occludin along isolated renal tubules. Kidney international 112 10844608
1997 Astrocytes increase barrier properties and ZO-1 expression in retinal vascular endothelial cells. Investigative ophthalmology & visual science 110 9344364
2016 ZO-1 interactions with F-actin and occludin direct epithelial polarization and single lumen specification in 3D culture. Journal of cell science 108 27802160
1989 ZO-1 and cingulin: tight junction proteins with distinct identities and localizations. The American journal of physiology 98 2679124
2018 ZIP4 Promotes Pancreatic Cancer Progression by Repressing ZO-1 and Claudin-1 through a ZEB1-Dependent Transcriptional Mechanism. Clinical cancer research : an official journal of the American Association for Cancer Research 90 29615456
2001 alpha-catenin-independent recruitment of ZO-1 to nectin-based cell-cell adhesion sites through afadin. Molecular biology of the cell 88 11408571
2018 The scaffolding protein ZO-1 coordinates actomyosin and epithelial apical specializations in vitro and in vivo. The Journal of biological chemistry 84 30242130
2014 Krüppel-like factor 4 regulates blood-tumor barrier permeability via ZO-1, occludin and claudin-5. Journal of cellular physiology 84 24318462
2001 The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins. The Journal of biological chemistry 82 11278603
2019 Inhibition of CREB-mediated ZO-1 and activation of NF-κB-induced IL-6 by colonic epithelial MCT4 destroys intestinal barrier function. Cell proliferation 81 31418947
2006 ZO-1 expression and phosphorylation in diabetic nephropathy. Diabetes 81 16567508
2005 HIV-1 Tat protein-induced alterations of ZO-1 expression are mediated by redox-regulated ERK 1/2 activation. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 77 15829913
2005 ZO-1 alters the plasma membrane localization and function of Cx43 in osteoblastic cells. Journal of cell science 77 15855237
2010 ZO-1 is involved in trophoblastic cell differentiation in human placenta. American journal of physiology. Cell physiology 73 20200207
2020 PIK3R3 regulates ZO-1 expression through the NF-kB pathway in inflammatory bowel disease. International immunopharmacology 72 32473571
2004 Association of paracellin-1 with ZO-1 augments the reabsorption of divalent cations in renal epithelial cells. The Journal of biological chemistry 66 15496416
2008 Zonula occludens-1 (ZO-1) is involved in morula to blastocyst transformation in the mouse. Developmental biology 65 18423437
2004 Tight junction proteins ZO-1, occludin, and claudins in developing and adult human perineurium. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 65 15258179
2005 WT1-interacting protein and ZO-1 translocate into podocyte nuclei after puromycin aminonucleoside treatment. American journal of physiology. Renal physiology 64 15798086
2008 Different expression of occludin and ZO-1 in primary and metastatic liver tumors. Pathology oncology research : POR 62 18386163
2008 ZO-1- and ZO-2-dependent integration of myosin-2 to epithelial zonula adherens. Molecular biology of the cell 60 18596233
1991 The tight-junction-specific protein ZO-1 is a component of the human and rat blood-brain barriers. Neuroscience letters 60 1922971
2014 The structural and functional organization of the podocyte filtration slits is regulated by Tjp1/ZO-1. PloS one 59 25184792
2002 Evidence for a functional interaction between cingulin and ZO-1 in cultured cells. The Journal of biological chemistry 57 12023291
2008 LXA4 stimulates ZO-1 expression and transepithelial electrical resistance in human airway epithelial (16HBE14o-) cells. American journal of physiology. Lung cellular and molecular physiology 56 18849442
2014 Endophilin-1 regulates blood-brain barrier permeability by controlling ZO-1 and occludin expression via the EGFR-ERK1/2 pathway. Brain research 55 24854121
2011 The single Drosophila ZO-1 protein Polychaetoid regulates embryonic morphogenesis in coordination with Canoe/afadin and Enabled. Molecular biology of the cell 54 21508316
2010 ZO-1 determines adherens and gap junction localization at intercalated disks. American journal of physiology. Heart and circulatory physiology 54 21131473
2001 Expression of ZO-1 and occludin in normal human placenta and in hydatidiform moles. Molecular human reproduction 54 11228248
1999 In vivo interaction of AF-6 with activated Ras and ZO-1. Biochemical and biophysical research communications 51 10334923
1995 Histamine, ZO-1 and increased blood-retinal barrier permeability in diabetic retinopathy. Transactions of the American Ophthalmological Society 51 8719694
2019 The Drosophila Afadin and ZO-1 homologues Canoe and Polychaetoid act in parallel to maintain epithelial integrity when challenged by adherens junction remodeling. Molecular biology of the cell 50 31188739
2019 Erythropoietin protects outer blood-retinal barrier in experimental diabetic retinopathy by up-regulating ZO-1 and occludin. Clinical & experimental ophthalmology 50 31483932
2015 ETB receptor-mediated MMP-9 activation induces vasogenic edema via ZO-1 protein degradation following status epilepticus. Neuroscience 49 26232046
1993 ZO-1 in corneal epithelium; stratal distribution and synthesis induction by outer cell removal. Experimental eye research 49 8224016
2015 The connexin 43/ZO-1 complex regulates cerebral endothelial F-actin architecture and migration. American journal of physiology. Cell physiology 48 26289751
2005 Glucose degradation products downregulate ZO-1 expression in human peritoneal mesothelial cells: the role of VEGF. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 48 15814533
2017 Roles of claudin-2, ZO-1 and occludin in leaky HK-2 cells. PloS one 46 29252987
2019 RBM47-regulated alternative splicing of TJP1 promotes actin stress fiber assembly during epithelial-to-mesenchymal transition. Oncogene 45 31358901
2006 Polychaetoid/ZO-1 is required for cell specification and rearrangement during Drosophila tracheal morphogenesis. Current biology : CB 45 16782014
1990 Characterization of the ZO-1 protein in endothelial and other cell lines. Journal of cell science 44 2277090
2017 Phosphorylation regulates connexin43/ZO-1 binding and release, an important step in gap junction turnover. Molecular biology of the cell 43 29021339
2006 ZO-1 is required for protein kinase C gamma-driven disassembly of connexin 43. Cellular signalling 43 17210245
2022 ZO-1 Guides Tight Junction Assembly and Epithelial Morphogenesis via Cytoskeletal Tension-Dependent and -Independent Functions. Cells 41 36497035
2024 Adaptive Metabolic Responses Facilitate Blood-Brain Barrier Repair in Ischemic Stroke via BHB-Mediated Epigenetic Modification of ZO-1 Expression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 39 38666466
2017 Estrogen decreases tight junction protein ZO-1 expression in human primary gut tissues. Clinical immunology (Orlando, Fla.) 39 28867253
2007 Identification, tissue distribution and developmental expression of tjp1/zo-1, tjp2/zo-2 and tjp3/zo-3 in the zebrafish, Danio rerio. Gene expression patterns : GEP 39 17632043
2019 Quantitative Phenotyping of Cell-Cell Junctions to Evaluate ZO-1 Presentation in Brain Endothelial Cells. Annals of biomedical engineering 38 30993538
2018 Decreased expression of ZO-1 is associated with tumor metastases in liver cancer. Oncology letters 38 30675248
2018 Whole-Exome Sequencing Identifies Pathogenic Variants in TJP1 Gene Associated With Arrhythmogenic Cardiomyopathy. Circulation. Genomic and precision medicine 37 30354300
2017 Dietary Tryptophan Enhanced the Expression of Tight Junction Protein ZO-1 in Intestine. Journal of food science 37 28125771
1999 Developmental expression of ZO-1 antigen in the mouse blood-brain barrier. Brain research. Developmental brain research 35 10320755
2022 Lipopolysaccharide downregulates the expression of ZO-1 protein through the Akt pathway. BMC infectious diseases 34 36199030
2018 Uremia Impacts VE-Cadherin and ZO-1 Expression in Human Endothelial Cell-to-Cell Junctions. Toxins 34 30301260
2020 Testin regulates the blood-testis barrier via disturbing occludin/ZO-1 association and actin organization. Journal of cellular physiology 33 31975378
2017 SHANK3 Regulates Intestinal Barrier Function Through Modulating ZO-1 Expression Through the PKCε-dependent Pathway. Inflammatory bowel diseases 33 28906292
2015 Characterization of genome-wide TFCP2 targets in hepatocellular carcinoma: implication of targets FN1 and TJP1 in metastasis. Journal of experimental & clinical cancer research : CR 33 25609232
2009 Up-regulation of ZO-1 expression and barrier function in cultured human corneal epithelial cells by substance P. FEBS letters 32 19446555
1995 Molecular environment of ZO-1 in epithelial and non-epithelial cells. Cell motility and the cytoskeleton 32 7553918
2022 Force-dependent remodeling of cytoplasmic ZO-1 condensates contributes to cell-cell adhesion through enhancing tight junctions. iScience 31 35198899
2017 ZO-1 expression is suppressed by GM-CSF via miR-96/ERG in brain microvascular endothelial cells. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 31 28430012
2015 ZO-1 and -2 Are Required for TRPV1-Modulated Paracellular Permeability. Journal of dental research 31 26464396
2002 Localization of ZO-1 and E-cadherin in the nasal polyp epithelium. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 31 12386748
2007 The proteasome regulates the interaction between Cx43 and ZO-1. Journal of cellular biochemistry 29 17541973
2022 Hydroxysafflor Yellow A Blocks HIF-1α Induction of NOX2 and Protects ZO-1 Protein in Cerebral Microvascular Endothelium. Antioxidants (Basel, Switzerland) 28 35453413
2001 Spatiotemporal expression of catenins, ZO-1, and occludin during early polarization of hepatic WIF-B9 cells. American journal of physiology. Cell physiology 28 11171572
2001 Characterization of the association of connexins and ZO-1 in the lens. Cell communication & adhesion 28 12064591
2022 Cingulin binds to the ZU5 domain of scaffolding protein ZO-1 to promote its extended conformation, stabilization, and tight junction accumulation. The Journal of biological chemistry 27 35259394
2017 Cell confluence regulates claudin-2 expression: possible role for ZO-1 and Rac. American journal of physiology. Cell physiology 27 29187366
2018 Effects of the differential expression of ZO-1 and ZO-2 on podocyte structure and function. Genes to cells : devoted to molecular & cellular mechanisms 24 29845705
1993 Altered expression and localization of the tight junction protein ZO-1 after common bile duct ligation. The American journal of physiology 24 8333499
2020 ZO-1 Regulates Intercalated Disc Composition and Atrioventricular Node Conduction. Circulation research 23 32347164
2020 IGF2BP3 and miR191-5p synergistically increase HCC cell invasiveness by altering ZO-1 expression. Oncology letters 23 32724385
2022 Circular RNA circCCNB1 inhibits the migration and invasion of nasopharyngeal carcinoma through binding and stabilizing TJP1 mRNA. Science China. Life sciences 21 35471687
2017 Targeting Neph1 and ZO-1 protein-protein interaction in podocytes prevents podocyte injury and preserves glomerular filtration function. Scientific reports 21 28935902
2024 ZO-1 interacts with YB-1 in endothelial cells to regulate stress granule formation during angiogenesis. Nature communications 20 38782923
2009 NHS-A isoform of the NHS gene is a novel interactor of ZO-1. Experimental cell research 20 19447104
2023 SHED-derived exosomes ameliorate hyposalivation caused by Sjögren's syndrome via Akt/GSK-3β/Slug-mediated ZO-1 expression. Chinese medical journal 19 37052137
2017 Binding of ZO-1 to α5β1 integrins regulates the mechanical properties of α5β1-fibronectin links. Molecular biology of the cell 19 28251923
2022 MicroRNA-155-5p inhibition alleviates irritable bowel syndrome by increasing claudin-1 and ZO-1 expression. Annals of translational medicine 18 36819593
2023 Hypoxic nasopharyngeal carcinoma-derived exosomal miR-455 increases vascular permeability by targeting ZO-1 to promote metastasis. Molecular carcinogenesis 17 36929868
2023 Loss of TJP1 disrupts gastrulation patterning and increases differentiation toward the germ cell lineage in human pluripotent stem cells. Developmental cell 17 37354899
2021 Hydrogen sulfide prevents ethanol-induced ZO-1 CpG promoter hypermethylation-dependent vascular permeability via miR-218/DNMT3a axis. Journal of cellular physiology 17 33855696
2015 Drug Transporters and Na+/H+ Exchange Regulatory Factor PSD-95/Drosophila Discs Large/ZO-1 Proteins. Pharmacological reviews 17 26092975
2020 The tight junction protein TJP1 regulates the feeding-modulated hepatic circadian clock. Nature communications 16 32001717
2020 CircSMC3 regulates gastric cancer tumorigenesis by targeting miR-4720-3p/TJP1 axis. Cancer medicine 16 32314520

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