| 1994 |
ZO-2 (TJP2) was found to coimmunoprecipitate with ZO-1 from MDCK cell extracts, identifying it as a tight junction-associated peripheral membrane protein that interacts with ZO-1. ZO-2 contains a region homologous to ZO-1 including guanylate kinase-like and PDZ domains (MAGUK family). ZO-2 localizes exclusively at cytoplasmic surfaces of tight junctions in epithelia (liver, intestine, kidney, testis, arterial endothelium) but is absent from the fascia adherens in cardiac myocytes, unlike ZO-1. |
Coimmunoprecipitation from MDCK cells, polyclonal antibody against unique ZO-2 region, immunohistochemistry of frozen tissue sections, double-label immunofluorescence |
The Journal of cell biology |
High |
8132716
|
| 1996 |
ZO-2 contains three PDZ domains, an SH3 domain, and a guanylate kinase-like domain. An alternatively spliced 36-amino acid domain exists in the C-terminal proline-rich region. The PDZ and protein-binding domains are highly conserved relative to ZO-1, while the C-terminal regions are divergent (25% identity), suggesting distinct functions. |
Full-length cDNA sequencing and sequence analysis of multiple ZO-2 cDNAs |
The Journal of biological chemistry |
Medium |
8824195
|
| 1999 |
ZO-2 binds directly to the COOH-terminal YV sequence of claudin-1 through -8 via its PDZ1 domain in vitro. In cells lacking ZO-1, ZO-2 is recruited to claudin-based networks through both PDZ2 (ZO-2)/PDZ2 (ZO-1) interactions and PDZ1 (ZO-2)/claudin-COOH interactions. |
In vitro binding assays with purified recombinant PDZ domains, transfection of claudins into L fibroblasts, immunofluorescence colocalization |
The Journal of cell biology |
High |
10601346
|
| 1999 |
ZO-2 directly binds F-actin in vitro (cosedimentation assay) but does not act as an F-actin cross-linking protein and does not bind actin filament ends. ZO-2 also directly binds ZO-1 and occludin. Immunoprecipitation showed ZO-1 and ZO-2 exist primarily as independent ZO-1·ZO-2 complexes rather than a trimeric ZO-1·ZO-2·ZO-3 complex in situ. |
Actin cosedimentation assays with purified recombinant proteins, low-speed sedimentation analyses, immunoprecipitation, immunofluorescence colocalization in cytochalasin D-treated MDCK cells |
The Journal of biological chemistry |
High |
10575001
|
| 1999 |
The NH2-terminal fragment of cingulin (residues 1-378) interacts in vitro with ZO-2 in pull-down assays from epithelial lysates. ZO-2 immunoprecipitates contain cingulin, confirming an in vivo interaction. |
Pull-down assays from epithelial and insect cell lysates, co-immunoprecipitation |
The Journal of cell biology |
Medium |
10613913
|
| 2000 |
Protein 4.1R isoforms (135 and 150 kDa) specifically interact with ZO-2 via residues encoded by exons 19-21 of 4.1R and residues 1054-1118 of ZO-2, as determined by yeast two-hybrid, in vitro binding, and co-immunoprecipitation. 4.1R co-localizes with ZO-2 and occludin at MDCK tight junctions and co-precipitates with ZO-2, ZO-1, occludin, actin, and alpha-spectrin, suggesting 4.1R links the tight junction to the actin cytoskeleton through ZO-2. |
Yeast two-hybrid system, in vitro binding studies, immunocolocalization, immunoprecipitation, Western blot |
The Journal of biological chemistry |
High |
10874042
|
| 2001 |
Adenovirus type 9 E4-ORF1 oncoprotein selectively targets ZO-2 (acting as a candidate tumor suppressor). Complex formation is mediated by the C-terminal PDZ-binding motif of Ad9 E4-ORF1 and the first PDZ domain of ZO-2. This interaction results in aberrant cytoplasmic sequestration of ZO-2. Overexpression of wild-type ZO-2 (but not mutant ZO-2 lacking PDZ2 and PDZ3) interfered with Ad9 E4-ORF1-induced focus formation. |
Co-immunoprecipitation, immunofluorescence colocalization, focus formation assay, ZO-2 overexpression/mutant rescue experiments |
The EMBO journal |
Medium |
11598001
|
| 2002 |
ZO-2 localizes to the nucleus in sparse epithelial cultures, accumulating in clusters that partially colocalize with splicing factor SC35. Nuclear staining diminishes as cultures reach confluence. Nuclear-to-cytoplasm shuttling is sensitive to leptomycin B (nuclear export inhibitor) and is mediated by the actin cytoskeleton. ZO-2 shuttling to the nucleus uses a pre-existing pool, not newly synthesized protein. |
Immunofluorescence in MDCK cells at varying confluence, leptomycin B treatment, mechanical injury assay, cell-cell contact disruption, protein synthesis inhibition |
Experimental cell research |
Medium |
11855865
|
| 2002 |
Nuclear ZO-2 directly interacts with the DNA-binding protein scaffold attachment factor-B (SAF-B) via its PDZ1 domain, as shown by yeast two-hybrid assays and in vivo co-immunoprecipitation. EGFP-ZO-2 and DsRed-SAF-B fusion proteins partially co-localize in nuclei of transfected epithelial cells. No association of SAF-B with ZO-1 was found. |
Yeast two-hybrid assay, co-immunoprecipitation from epithelial cells, confocal microscopy of fluorescently-tagged fusion proteins |
The Journal of biological chemistry |
Medium |
12403786
|
| 2003 |
A mutation in the first PDZ domain of TJP2/ZO-2 (associated with familial hypercholanemia in Amish individuals) reduces PDZ1 domain stability and ligand binding in vitro. Hepatic tight junctions show a morphological change in individuals with this mutation. |
In vitro domain stability and ligand binding assays with recombinant PDZ1 domain mutant, electron microscopy of liver biopsies |
Nature genetics |
Medium |
12704386
|
| 2003 |
Tyrosine phosphorylation of the C-terminal tail of occludin (by c-Src in vitro) markedly reduces its binding to ZO-2 (as well as ZO-1 and ZO-3), but does not affect occludin binding to F-actin. |
In vitro phosphorylation of GST-fused C-occludin by c-Src, in vitro binding assays with ZO-2 |
Biochemical and biophysical research communications |
Medium |
12604349
|
| 2004 |
ZO-2 associates with transcription factors Jun, Fos, and C/EBP both at the nucleus and at tight junction regions of epithelial cells. This association was confirmed by pull-down assays, gel shift analysis, and co-immunoprecipitation. ZO-2 down-regulates AP-1-controlled gene transcription in a dose-dependent manner; both the amino and carboxyl domains of ZO-2 are capable of inhibiting gene transcription. |
Pull-down assays with ZO-2 GST fusion proteins, gel shift (EMSA), co-immunoprecipitation, immunolocalization, CAT reporter gene assays |
Experimental cell research |
Medium |
14720506
|
| 2004 |
ZO-2 is present in the nuclear matrix and co-immunoprecipitates with lamin B1 and actin from nuclei of sparse cultures. ZO-2 contains multiple nuclear localization signals (NLS) at its amino region; deletion of these NLS diminishes nuclear import and impairs the ability to regulate AP-1-controlled transcriptional activity. ZO-2 contains a functional nuclear export signal (NES2) at the GK region that is leptomycin B-sensitive. |
Nuclear fractionation, co-immunoprecipitation from nuclear fractions, NLS deletion mutants transfection, nuclear export assay with ovalbumin-conjugated NES peptides, leptomycin B sensitivity, reporter gene assay |
Experimental cell research |
Medium |
15194440
|
| 2004 |
ARVCF interacts with ZO-2 via a C-terminal PDZ-binding motif on ARVCF and the PDZ domains of ZO-2. Nuclear localization of ARVCF is dependent on this PDZ-binding motif and can be mediated specifically by the PDZ domains of ZO-2 (but not equivalently by ZO-1). Disruption of cell-cell adhesion releases ARVCF from the plasma membrane, with an increased fraction localizing to the nucleus. |
Co-immunoprecipitation, yeast two-hybrid, fluorescence microscopy, domain-mapping using PDZ-binding motif mutants, calcium-switch assay |
Molecular biology of the cell |
Medium |
15456900
|
| 2005 |
hScrib (mammalian Scribble homolog) directly interacts with ZO-2 via two PDZ domains of hScrib and the C-terminal PDZ-binding motif of ZO-2. Both proteins colocalize at cell-cell junctions. A point mutation in the LRR of hScrib delocalizes it from the plasma membrane and abrogates the interaction with ZO-2. |
GST pull-down, co-immunoprecipitation, immunofluorescence colocalization, LRR point-mutant analysis |
FEBS letters |
Medium |
15975580
|
| 2006 |
ZO-1 and ZO-2 independently determine where claudins are polymerized during tight junction strand formation. In cells lacking both ZO-1 and ZO-2 (ZO-1 knockout/ZO-2 knockdown), tight junctions are completely absent despite normal cell polarity. Re-expression of either ZO-1 or ZO-2 alone restores claudin polymerization and tight junction formation. A truncated ZO-1 containing only PDZ1-3 was insufficient; forced membrane recruitment and dimerization of this truncated form restored claudin polymerization. |
Homologous recombination, RNAi knockdown, exogenous rescue by transfection, immunofluorescence, transepithelial resistance measurement |
Cell |
High |
16923393
|
| 2006 |
ZO-2 contains four nuclear export signals (NES-0, NES-1 in PDZ2; NES-2, NES-3 in GK region). NES-0 and NES-3 are functional and leptomycin B-sensitive. NES-1, previously thought non-functional, becomes active upon acquisition of negative charge at Ser369. Efficient nuclear exit of ZO-2 amino and middle segments requires paired NES; mutation of any single NES in full-length ZO-2 induces nuclear accumulation. |
Nuclear export assay using ovalbumin-conjugated NES peptides microinjected into nuclei of MDCK cells, leptomycin B sensitivity, transfection of full-length ZO-2 NES mutants |
Experimental cell research |
Medium |
16920099
|
| 2007 |
ZO-2 silencing in MDCK cells increases paracellular permeability to dextran (gate function impairment), disrupts fence function (non-polarized E-cadherin distribution), decreases occludin and E-cadherin protein levels, delays arrival of ZO-1, occludin and E-cadherin to the plasma membrane during calcium switch, and produces atypical monolayer architecture with widened intercellular spaces, multistratification, and altered actin patterns. |
siRNA knockdown in MDCK cells, transepithelial electrical resistance measurement, dextran flux assay, calcium switch assay, immunofluorescence, Western blot |
Experimental cell research |
Medium |
17374535
|
| 2007 |
ZO-2 down-regulates cyclin D1 transcription in a dose-dependent manner via an E box in the cyclin D1 promoter, reducing cell proliferation. ZO-2 does not directly bind DNA but recruits c-Myc (confirmed by EMSA, ChIP, and co-immunoprecipitation) and HDAC1 to the E box. HDAC activity is required for ZO-2-mediated repression. |
CAT reporter gene assays with cyclin D1 promoter deletions, EMSA, chromatin immunoprecipitation (ChIP), co-immunoprecipitation, HDAC inhibitor treatment, wound-healing proliferation assay |
Molecular biology of the cell |
High |
17881732
|
| 2008 |
ZO-2 knockout mice die shortly after implantation due to arrest in early gastrulation, demonstrating a non-redundant and critical role of ZO-2 in mammalian development. ZO-2−/− embryos show decreased proliferation at E6.5, increased apoptosis at E7.5, altered apical junctional complex architecture, and increased paracellular permeability. ZO-3 knockout mice have no obvious phenotype, indicating ZO-3 is dispensable. |
Gene targeting (ZO-2 and ZO-3 knockout mice), embryo histology and immunohistochemistry, paracellular tracer permeability assay, TUNEL/BrdU assays |
Molecular and cellular biology |
High |
18172007
|
| 2008 |
ZO-1 and ZO-2 are both required for integration of myosin-2 into the epithelial zonula adherens (ZA). In ZO-1/ZO-2 double-depleted cells, a fragmented adherens junction (prezonula-AJ) positive for E-cadherin and actin but negative for myosin-2 forms. Re-expression of full-length ZO-1 or ZO-2 (or ZO-1 lacking PDZ1/2 but not PDZ1/2/3) restores myosin-2 integration. ZO-1/ZO-2 regulate RhoA-dependent spatiotemporal Rho activation for ZA establishment. |
Conditional ZO-1 KO/ZO-2 KD cell lines, rescue by transfection of truncation mutants, immunofluorescence, FRET analysis of Rho activation, dominant-active RhoA/ROCK transfection |
Molecular biology of the cell |
High |
18596233
|
| 2008 |
In mouse preimplantation embryos, ZO-2 is expressed from both maternal and embryonic genomes; maternal ZO-2 protein associates with nuclei in zygotes and early cleavage stages. ZO-2 siRNA knockdown in zygotes delayed blastocoel cavity formation but did not block cell proliferation. ZO-2-deficient embryos compensatorily increased ZO-1 (but not occludin) assembly at tight junctions. |
siRNA microinjection into mouse zygotes/2-cell embryos, immunofluorescence, quantitative junctional analysis, blastocoel measurement |
Experimental cell research |
Medium |
18817772
|
| 2010 |
ZO-2 uses its first PDZ domain to form a complex with YAP2. Endogenous ZO-2 and YAP2 co-localize in the nucleus. ZO-2 facilitates the nuclear localization and pro-apoptotic function of YAP2 in a PDZ-domain-dependent manner. |
Co-immunoprecipitation, co-localization by immunofluorescence, PDZ-domain deletion mutant analysis, nuclear localization and apoptosis assays |
The Biochemical journal |
Medium |
20868367
|
| 2010 |
Genomic duplication of TJP2 in a family with progressive nonsyndromic hearing loss DFNA51 leads to overexpression of TJP2 transcript and protein. TJP2 overexpression in affected family members leads to decreased phosphorylation of GSK-3β and altered expression of apoptosis-regulating genes, suggesting a mechanism for progressive hair cell death. |
SNP array genomic analysis, RT-PCR, Western blot, immunohistochemistry of inner ear tissue, phospho-GSK-3β Western blot, expression profiling of apoptosis genes |
American journal of human genetics |
Medium |
20602916
|
| 2013 |
JAM-A directly associates with ZO-2 (and indirectly with afadin), and this complex together with PDZ-GEF1 activates the small GTPase Rap2c. siRNA-mediated downregulation of JAM-A, ZO-2, afadin, or PDZ-GEF1 results in enhanced epithelial permeability, indicating ZO-2 is a functional component of the JAM-A/afadin/PDZ-GEF1/Rap2c signaling module that regulates barrier function. |
Co-immunoprecipitation, siRNA knockdown, transepithelial resistance and permeability assays, GTPase activity assays |
Molecular biology of the cell |
Medium |
23885123
|
| 2013 |
SNX27 interacts with ZO-2 via the PDZ domain of SNX27 and the C-terminal PDZ-binding motif of ZO-2. Upon tight junction disruption by calcium chelation, ZO-2 transiently localizes to SNX27-positive early endosomes. SNX27 depletion decreases ZO-2 (but not ZO-1) mobility at cell-cell contacts (FRAP) and increases junctional permeability to large solutes. |
Proteomic interaction screen, co-immunoprecipitation, confocal immunofluorescence, FRAP, siRNA knockdown, permeability assays |
The Biochemical journal |
Medium |
23826934
|
| 2014 |
Protein-truncating mutations in TJP2 cause failure of protein localization to tight junctions and disruption of tight-junction structure, resulting in severe progressive cholestatic liver disease. This contrasts with embryonic-lethal knockout in mice, highlighting species and organ-specific redundancy differences. |
Next-generation sequencing, immunohistochemistry and electron microscopy of liver biopsies, protein localization studies in patient tissue |
Nature genetics |
High |
24614073
|
| 2016 |
ZO-2 silencing in MDCK renal epithelial cells induces cell hypertrophy via two mechanisms: (1) prolonging G1 phase due to elevated cyclin D1, and (2) augmenting protein synthesis via nuclear accumulation and increased transcriptional activity of YAP, which decreases PTEN expression, elevating PIP3 and activating Akt/mTOR/S6K1 signaling. In uninephrectomized rats, compensatory renal hypertrophy is accompanied by decreased ZO-2 and nuclear YAP expression. |
siRNA knockdown in MDCK cells, cell cycle analysis, protein synthesis measurement, YAP localization and activity assays, PTEN/Akt/mTOR/S6K1 Western blot, uninephrectomy rat model, immunofluorescence |
Molecular biology of the cell |
High |
27009203
|
| 2016 |
ZO-2 is SUMOylated by the SUMO machinery; it associates with E2 SUMO-conjugating enzyme Ubc9 and SUMO-deconjugating proteases SENP1 and SENP3. SUMOylation site K730 in human ZO-2 (GuK domain) was identified; mutation K730R results in prolonged nuclear localization. A construct mimicking constitutive SUMOylation (SUMO1ΔGG-ZO-2) localizes preferentially to the cytoplasm. ZO-2 directly binds GSK3β, and cytosolic SUMO1ΔGG-ZO-2 modulates GSK3β kinase activity. ZO-2 also forms a complex with β-catenin, and wild-type ZO-2 inhibits β-catenin/TCF-4 transcriptional activity. |
Co-immunoprecipitation, Ubc9 fusion-directed SUMOylation, SENP1 inhibition assays, site-directed mutagenesis (K730R), nuclear recruitment assay, reporter gene assay, GSK3β kinase activity assay |
Cellular and molecular life sciences |
Medium |
27604867
|
| 2018 |
The organophosphate pesticide methamidophos (MET) forms covalent bonds with ZO-2 at serine, tyrosine, and lysine residues. MET induces phosphorylation of ZO-2 and reduces the interaction between ZO-2 and occludin. MET targets ubiquitination sites on ZO-2 (including a lysine residue), and mutation of a MET-target lysine residue in ZO-2 interferes with TJ sealing in epithelial cells. |
Mass spectrometry (covalent modification identification), co-immunoprecipitation, Western blot (phosphorylation), transfection of ZO-2 mutants into epithelial cells, transepithelial resistance measurement |
Toxicology and applied pharmacology |
Medium |
30291936
|
| 2019 |
CaSR activation by Gd3+ triggers ZO-2 concentration at tight junctions via PKC activation, which phosphorylates and activates WNK4, which in turn phosphorylates ZO-2, inducing its TJ localization. In low calcium, ZO-2 is protected from degradation by association with 14-3-3 proteins (ζ and σ). The ZO-2/14-3-3 complexes move to cell borders upon calcium restoration and then dissociate. The unique region 2 of ZO-2 and S261 (within an NLS) are critical for the interaction with 14-3-3 proteins and for efficient nuclear importation. |
Co-immunoprecipitation, pharmacological inhibition (CaSR agonist Gd3+, PKC/WNK4 inhibitors), site-directed mutagenesis (S261 and unique region 2 mutants), immunofluorescence, Western blot |
Molecular biology of the cell |
Medium |
31318316
|
| 2021 |
ZO-2 tight junction protein modulates nuclear accumulation of TEAD transcription factor. ZO-2 knockdown reduces nuclear TEAD; ZO-2 lacking NLS does not facilitate TEAD nuclear entry. Inhibition of nPKCδ in parental cells triggers cytoplasmic ZO-2/TEAD interaction and facilitates ZO-2/TEAD complex nuclear importation. nPKCε activates a ZO-2 nuclear export signal to enhance TEAD nuclear exit. ZO-2/TEAD interaction was confirmed by proximity ligation, co-immunoprecipitation, and pull-down assays. |
Proximity ligation assay, co-immunoprecipitation, pull-down assay, nPKCδ/ε inhibitor treatment, ZO-2 NLS mutant transfection, immunofluorescence of TEAD localization |
Molecular biology of the cell |
Medium |
34010016
|
| 2021 |
Liver-specific deletion of Tjp2 in mice results in lower claudin-1 protein levels, dilated canaliculi, lower microvilli density, aberrant radixin and BSEP (Abcb11) distribution, and mild progressive cholestasis with reduced Abcb11/Bsep and Cyp2b10 expression. Cholic acid diet causes severe cholestasis and liver necrosis in Tjp2-deficient mice. Combined hepatocyte and cholangiocyte deletion was necessary for severe CA-induced injury. |
Conditional liver-specific Cre-lox knockout (hepatocyte-specific and cholangiocyte-specific), electron microscopy, immunostaining, biochemical analysis, FITC-dextran permeability assay, cholic acid diet challenge |
Gastroenterology |
High |
33465371
|
| 2021 |
ZO-2 associates with LATS1 (Hippo kinase), functioning as a scaffold for the Hippo pathway. ZO-2 silencing is accompanied by diminished LATS activity and nuclear concentration of YAP in renal epithelial cells, in uninephrectomized rat kidneys, and in liver steatosis in obese Zucker rats. |
Co-immunoprecipitation (ZO-2/LATS1), immunofluorescence of YAP localization, LATS kinase activity assay, siRNA knockdown, in vivo uninephrectomy rat model, obese Zucker rat model |
Tissue barriers |
Medium |
34689705
|
| 2022 |
Liver-specific Tjp2 deletion in mice leads to DDC-diet-induced hepatocyte-to-cholangiocyte transdifferentiation, which is Yap/Wwtr1(Taz)-dependent and cell-autonomous to hepatocytes (not cholangiocytes). Tjp2 inactivation is sufficient to upregulate Yap and Taz protein expression in hepatocytes, but efficient transdifferentiation additionally requires the DDC-diet insult. Notch2 is not required. |
Conditional Tjp2 KO (hepatocyte-specific and cholangiocyte-specific), DDC diet challenge, Yap/Taz genetic inactivation experiments, immunostaining, lineage tracing |
NPJ Regenerative medicine |
Medium |
36151109
|
| 2022 |
Residues K759 and K992 in human ZO-2 are acceptors for K48-linked polyubiquitination (targeting for proteasomal degradation); mutation to arginine increases ZO-2 half-life from ~20 to ~37 h. Residue K730 (the SUMOylation site) mutation increases ubiquitination and decreases ZO-2 half-life to ~6.7 h. Mutations at K759, K992, or K730 all decrease the TJ sealing peak (transepithelial resistance). |
Co-immunoprecipitation with ubiquitin antibodies, TUBE (tandem ubiquitin-binding entity) assay for K48-polyubiquitin, site-directed mutagenesis of K730, K759, K992, half-life measurement by cycloheximide chase, transepithelial resistance measurement |
Cells |
Medium |
36291162
|
| 2023 |
ZNF582 binds to TJP2/ZO-2 protein and upregulates TJP2 protein expression. Increased TJP2 combines with ERK2 to promote ERK2 protein expression and suppresses phosphorylation of ERK2, thereby inhibiting ccRCC growth and metastasis. |
TMT quantitative proteomics, co-immunoprecipitation, Western blot, cell phenotype and orthotopic tumor experiments |
Cell death & disease |
Medium |
36966163
|
| 2023 |
p190A RhoGAP interacts with ZO-2 in a manner dependent on RasGAP. Both RasGAP and ZO-2 are required for p190A to activate LATS kinases, elicit mesenchymal-to-epithelial transition, promote contact inhibition, suppress tumorigenesis, and transcriptionally modulate target genes. Low ARHGAP35 expression combined with high TJP2 expression predicts shorter survival. |
Co-immunoprecipitation, siRNA knockdown of ZO-2/RasGAP, LATS kinase activity assay, cell proliferation/contact inhibition assays, in vivo tumorigenesis models, reporter gene assay |
Cell reports |
Medium |
37995182
|
| 2024 |
ZO-2 is required for contact-mediated inhibition of proliferation. ZO-2 acts as a scaffold that promotes LATS1-YAP interaction: ZO-2 binds LATS1 via its SH3 domain and YAP via its PDZ domains, thereby facilitating LATS1-mediated phosphorylation of YAP, leading to YAP cytoplasmic retention and inactivation. ZO-2 also promotes LATS1 stability. |
Co-immunoprecipitation with domain-specific ZO-2 mutants (SH3 and PDZ domain mutations), YAP phosphorylation assay, cell proliferation/contact inhibition assays, LATS1 stability measurement |
The FEBS journal |
Medium |
39462647
|
| 2024 |
ZO-2 loss reduces apical membrane rigidity (measured by AFM), inhibits γ-actin and JAM-A recruitment to the cell border, and facilitates p114RhoGEF and afadin accumulation at junctions, leading to increased TJ mechanical tension (measured by FRET ZO-1 tension probe) and increased tricellular TJ tension. ZO-2 KD cells show impaired responses to substrate stiffness and topography, and increased nuclear YAP and Snail. |
Atomic force microscopy, FRET tension probes (ZO-1 and E-cadherin), immunofluorescence, siRNA knockdown, AFM membrane rigidity measurement, nanostructured substrate assays |
International journal of molecular sciences |
Medium |
38473701
|
| 2025 |
ZO-2 colocalizes with CEP164 at the distal appendage of the mother centriole and is present at mitotic spindle poles, the basal body of primary cilia, and the tail of spermatozoa. ZO-2 depletion inhibits astral and mitotic spindle microtubule (EB1-expressing) development, reduces KIF14 and TPX2 at spindle poles, increases NuMA accumulation, and decreases p-Aurora levels, leading to reduced spindle length, microtubule instability, and abnormal chromosome congression. ZO-2 co-immunoprecipitates with KIF14, NuMA, and p-Aurora; NuMA and Aurora-A bind different segments of ZO-2. ZO-2 depletion also reduces primary cilium development and blocks Sonic Hedgehog signaling. |
Co-immunoprecipitation with ZO-2 segments, immunofluorescence colocalization, siRNA knockdown, spindle length and morphology analysis, EB1 live imaging, SHH reporter assay |
Cell and tissue research |
Medium |
40728639
|
| 2025 |
c-Abl kinase directly binds to and phosphorylates the C-terminus of ZO-2, and also stimulates JAK1, which subsequently phosphorylates the N-terminus of ZO-2. c-Abl regulates cellular morphology and migration through ZO-2 phosphorylation (demonstrated by RNAi knockdown/rescue strategy). c-Abl activity is associated with decreased traction forces on the substrate. |
In vitro kinase assay (c-Abl phosphorylation of ZO-2 C-terminus), immunoprecipitation of c-Abl/ZO-2 complex, RNAi knockdown/rescue, traction force microscopy, cell migration assay |
FASEB journal |
Medium |
41259016
|
| 2026 |
ZO-2 directly binds to NTCP (the HBV receptor sodium taurocholate cotransporting polypeptide), and this interaction is required for NTCP cell surface localization. ZO-2 knockdown or knockout decreases NTCP at the cell surface, reducing HBV attachment and infection. HBV surface protein preS1 binding causes dissociation of the NTCP/ZO-2 complex and formation of NTCP-preS1-actin complexes that internalize into cells. Actin polymerization is required for preS1 internalization and HBV infection (latrunculin A blocks this). ZO-1 and ZO-3 knockdown had no effect on HBV infection. |
Immunopurification/LC-MS/MS (interaction discovery), co-immunoprecipitation, ZO-2 KD/KO, NTCP cell surface flow cytometry, HBV infection assay, preS1 binding assay, latrunculin A treatment |
mBio |
Medium |
41870046
|