Disease relevance of OCLN

• No statistical differences were detected for OCLN and CLDN-3 between the edema group and healthy controls [1].
• There was a significantly elevated expression (p<0.01) on mRNA and protein level between the leg ulcer group and healthy controls for OCLN and CLDN-3 [1].
• We first compared the expression of MT1-MMP and the localization of occludin/ZO-1 complexes in breast tumor cell lines displaying various degrees of invasiveness [2].
• Expression of ZO-1 and occludin in normal human placenta and in hydatidiform moles [3].
• Claudins 1, 4, 5, 7 and occludin in ameloblastomas and developing human teeth [4].

High impact information on OCLN

• The development of these junctions seems to depend on two primary processes: the appearance of high levels of the tight junction protein occludin and intracellular signaling processes that control the state of phosphorylation of junctional proteins [5].
• Occludin and claudins in tight-junction strands: leading or supporting players [6]?
• Overexpression increased the complexity of tight junction strands visible by freeze-fracture microscopy without affecting the levels of claudin-1, -2, or -3, occludin, or ZO-1 [7].
• In confluent airway epithelial cells, Der p 1 led to cleavage of the TJ adhesion protein occludin [8].
• Leaky epithelium in gammadelta(+) iIEL-deficient mice was associated with the absence of phosphorylation of serine residues of occludin and lack of claudin 3 and zona occludens-1 proteins in TJ complexes [9].

Psychiatry related information on OCLN

• Our findings could be important in unravelling new pathogenic pathways in dementia disorders and new functions of occludin and TJs [10].

Chemical compound and disease context of OCLN

• This study shows that 17-beta-estradiol can induce concentration- and time-related biphasic effects on tight junction functions expression of occludin in endothelial cells and that this perturbation of tight junction functions may have implications in the etiology of mastalgia and the vascular spread of breast cancer [11].
• CONCLUSIONS: Our studies support that activation of VEGFR-1, VEGFR-2, and IGF-IR by high glucose contributes to disruption of tight junctions by decreasing occludin expression and may be important in the pathogenesis of blood-retinal barrier dysfunction in diabetic retinopathy [12].

Biological context of OCLN

• Further transfection studies with various deletion mutants showed that the domain E, especially its COOH-terminal approximately 150 amino acids (domain E358/504), was necessary for the localization of occludin at TJ [13].
• Binding of an antibody to the first of the putative extracellular loops of occludin confirmed that this sequence was exposed on the cell surface, and synthetic peptides containing the amino acid sequence of this loop inhibit adhesion induced by occludin expression [14].
• In the present study, we expressed occludin under an inducible promotor in occludin-null fibroblasts to determine whether this protein confers intercellular adhesion [14].
• These results suggest that the extracellular surface of occludin is directly involved in cell-cell adhesion and the ability to confer adhesiveness correlates with the ability to colocalize with its cytoplasmic binding protein, ZO-1 [14].
• While the N-terminal extracellular domains of occludin mediate homotypic adhesion, the distal C-terminal cytoplasmic domain of occludin controls protein targeting and endocytosis [15].

Anatomical context of OCLN

• Furthermore, dendritic cells (DCs) of the medulla, with a major role for selection of thymocytes, expressed CLDN-1 and OCLN as well, implying that the interposition of DCs within the mTEC scaffold is also helped by TJs [16].
• Occludin is an integral membrane protein localizing at tight junctions (TJ) with four transmembrane domains and a long COOH-terminal cytoplasmic domain (domain E) consisting of 255 amino acids [13].
• Immunofluorescence and laser scan microscopy revealed that chick full-length occludin introduced into human and bovine epithelial cells was correctly delivered to and incorporated into preexisting TJ [13].
• The coincidence of the sequence necessary for the ZO-1 association with that for the TJ localization suggests that the association with underlying cytoskeletons through ZO-1 is required for occludin to be localized at TJ [13].
• Furthermore, neither endogenous occludin nor claudin is required for targeting to ZO-1-containing cell-cell contacts, since in normal rat kidney fibroblasts targeting of chimeras again required only the ZO-binding domain [17].

Associations of OCLN with chemical compounds

• Tight junction disassembly was manifest by a reduction in the expression of Triton-soluble occludin and ZO-1 by Western analysis and their disassociation manifested by immunostaining and confocal microscopy [18].
• Occludin proteolysis and increased permeability in endothelial cells through tyrosine phosphatase inhibition [19].
• PAO treatment lead to progressive disappearance of occludin from the cell periphery [19].
• Oxidative stress also reduced the co-immunoprecipitation of ZO-1 with occludin, which was prevented by genistein [20].
• Polyamine depletion by alpha-difluoromethylornithine (DFMO) decreased levels of occludin protein but failed to affect expression of its mRNA [21].
• Western immunoblot analysis of RRV-infected cells showed a significant fall in the levels of the nonphosphorylated form of occludin in both Triton X-100-insoluble and Triton X-100-soluble fractions, without any change in the levels of the phosphorylated form of occludin [22].

Physical interactions of OCLN

• Pair-wise binding studies using recombinant proteins demonstrated that ERK1 directly interacts with the C-terminal tail of occludin [23].
• Nonreceptor tyrosine kinase c-Yes interacts with occludin during tight junction formation in canine kidney epithelial cells [24].
• JRAB/MICAL-L2 Is a Junctional Rab13-binding Protein Mediating the Endocytic Recycling of Occludin [25].
• We have identified casein kinase I epsilon (CKI epsilon) as a binding partner for the C-terminal cytoplasmic domain of occludin by yeast two-hybrid screening [26].

Enzymatic interactions of OCLN

• EGF rapidly increased the levels of phosphorylated MEK (p-MEK) in detergent-soluble fractions and phosphorylated ERK (p-ERK) in detergent-insoluble fractions. p-ERK was colocalized and co-immunoprecipitated with occludin [23].
• S. flexneri serotype 2a and 5, but not the non-invasive Escherichia coli strain F-18, share the ability to regulate expression of ZO-1, ZO-2, E-cadherin and to dephosphorylate occludin [27].
• CKI epsilon phosphorylated occludin and co-localised and co-immunoprecipitated with occludin from human endothelial cells [26].

Co-localisations of OCLN

• Double immunolabelings showed that a fraction of endocytosed occludin was colocalized with Rab13 in MTD-1A cells [28].
• Moreover, we demonstrate in this study that occludin was colocalized with the nonreceptor tyrosine kinase c-Yes at cell junction areas and formed an immunoprecipitable complex with c-Yes in vivo [24].
• Antibodies to the human VAP-33 co-localized with occludin at the tight junction in many tissues and tissue culture cell lines [29].

Regulatory relationships of OCLN

• EGF also prevented H2O2-induced disruption of the actin cytoskeleton and the dissociation of occludin and ZO-1 from the actin-rich detergent-insoluble fractions [23].
• In human umbilical vein endothelial cells (HUVECs) the PTP inhibitors phenylarsine oxide (PAO) and pervanadate induced proteolysis of the tight junction protein occludin [19].
• MEK1/2 inhibitor U0126 significantly induced the expression of occludin at the cell-cell junction and substantially suppressed the p-MEK1/2 and p-ERK1/2 expressions in PC-1.0 and AsPC-1 cells [30].
• Unlike the parent OSE cell line, which had undergone a typical mesenchymal transformation in culture, E-cadherin-expressing cells contained cytokeratins and the tight-junction protein occludin [31].
• The rates of recovery of resistance, increase in barrier to inulin, and reorganization of occludin and ZO-1 into the intercellular junctions during the calcium-induced reassembly of tight junction were much greater in Caco-2 cells transfected with c-SrcK297R as compared with those in cells transfected with empty vector or wild type c-Src [32].
• Raf 1 inhibited occludin transcription by repressing a minimal segment of the occludin promoter in concert with upregulation of the transcriptional repressor, Slug without influencing the well-documented transcriptional repressor, Snail [33].
• Site-directed mutagenesis of the HSF-1 binding motif in the occludin promoter region inhibited HS-induced binding of HSF-1 to the occludin promoter region and subsequent promoter activity [34].

Other interactions of OCLN

• We concluded that occludin itself can localize at TJ and directly associate with ZO-1 [13].
• The cellular changes contributing to the increased permeability and increased na??ve monocyte transendothelial migration include the disruption of actin stress fiber formation and the decreased expression of lateral junction proteins (occludin and vascular endothelial cadherin) [35].
• In studies of human premature infants, we used immunomicroscopy to determine if amounts of the TJ proteins ZO-1, claudin and occludin increase with gestational age in vessels of germinal matrix (GM) and cortex [36].
• Immunostaining for occludin, claudins 1 and 5 and VE-cadherin was carried out on fixed tissue [37].
• Occludin staining was seen at the junctional complex, where it was not continuous, but dotted along the cell junctions.The transcripts for claudin-1 and several other claudin isotypes, such as -2, -3, -4, -7, -9 and -14 were identified [38].

Analytical, diagnostic and therapeutic context of OCLN

• Tight junction components were analysed by Western blots of occludin and zonula occludens [39].
• Using in vitro binding studies and site-directed mutagenesis, we have identified a large positively charged surface that contains the binding site for ZO-1, and this surface is required for proper localization of occludin to cell-cell junctions [15].
• Using RT-PCR techniques, we have identiried mRNAs encoding protein ZO-1, occludin and claudins 1, 4, 7, 8, 11, 12, and 17 in both tissues, skin and cultured keratinocytes, whereas claudins i and 10 have only been detected in skin tissue [40].
• Crystallization and preliminary X-ray diffraction of the ZO-binding domain of human occludin [41].
• Immunogold electron microscopy revealed occludin and caveolin-1 internalization in endosomal/caveolar-like structures in CNF-treated cells [42].

References