Disease relevance of OCLN

• Distinct effects of Vibrio cholerae haemagglutinin/protease on the structure and localization of the tight junction-associated proteins occludin and ZO-1 [1].

High impact information on OCLN

• The tight junction components ZO-1, ZO-2, endogenous ZO-3, and occludin were mislocalized during the early stages of tight junction assembly [2].
• NZO-3 expression did not alter expression levels of ZO-1, ZO-2, endogenous ZO-3, occludin, or E-cadherin; however, the amount of Triton X-100-soluble, signaling-active beta-catenin was increased in NZO-3-expressing cells during junction assembly [2].
• In vitro binding experiments showed that ZO-1 and actin preferentially bind to NZO-3, whereas both NZO-3 and the carboxy-terminal half of the molecule (CZO-3) contain binding sites for occludin and cingulin [2].
• In cultured monolayers of pure W cells, ouabain triggers the "P-->A mechanism" (from pump/adhesion) consisting of a cascade of phosphorylations that retrieves adhesion-associated molecules occludin and beta-catenin and results in detachment of the cell [3].
• Inhibition of membrane traffic with 0.4 M sucrose also blocked occludin internalization and TER loss [4].

Biological context of OCLN

• The effects of transfected occludin mutants on neutrophil migration did not correlate with their effects on selective paracellular permeability and transepithelial electrical resistance [5].
• Inhibition of caveolae-mediated endocytosis by cholesterol extraction prevented both LatA-induced TER loss and occludin internalization [4].
• The tyrosine kinase inhibitors genistein and PP-2 inhibited the recovery of transepithelial resistance and perturbed the relocalization of ZO-1 and occludin to the tight junction, indicating that tyrosine kinases, possibly members of the Src family, are critical for reassembly after oxidative stress [6].
• Our study demonstrates that down-regulation of the MAPK signaling pathway causes the restoration of epithelial cell morphology and the assembly of tight junctions in Ras-transformed epithelial cells and that tyrosine phosphorylation of occludin and ZO-1 may play a role in some aspects of tight junction formation [7].
• A similar pattern of zonula occludens-1 immunoreactivity was found in the cytoplasm of Sertoli cells, suggesting that occludin was not confined to the inter-Sertoli junctional areas and that subcellular localization of occludin in the Sertoli cells was dynamically regulated during spermatogenesis in canine testis [8].

Anatomical context of OCLN

• In the Madin-Darby canine kidney epithelial cell line, the proteins occludin and ZO-1 are structural components of the tight junctions that seal the paracellular spaces between the cells and contribute to the epithelial barrier function [7].
• Hence, specific domains and functional properties of occludin modulate transepithelial migration of neutrophils [5].
• After treatment of the Ras-transformed cells with the mitogen-activated protein kinase kinase (MEK1) inhibitor PD98059, which blocks the activation of mitogen-activated protein kinase (MAPK), occludin, claudin-1, and ZO-1 were recruited to the cell membrane, tight junctions were assembled, and E-cadherin protein expression was induced [7].
• In Ras-transformed Madin-Darby canine kidney cells, occludin, claudin-1, and ZO-1 were absent from cell-cell contacts but were present in the cytoplasm, and the adherens junction protein E-cadherin was weakly expressed [7].
• Moreover, the apical structure of filamentous actin (F-actin) was disturbed and tight junction-associated proteins (ZO-1 and occludin) were dispersed along the basolateral membranes [9].

Associations of OCLN with chemical compounds

• Western blot analysis showed that occludin bands of 66-85 kDa were digested by HA/P to two predominant bands of around 50 kDa and 35 kDa, and that this degradation was greatly attenuated when the specific bacterial metalloproteinase inhibitor Zincov was co-administered [1].
• Diatrizoate, and to a lesser extent ioxaglate, reduced the number of viable MDCK cells and showed a redistribution of the E-cadherin, ZO-1 and occludin immunofluorescence signal with a parallel decrease of the TMR indicating an impaired monolayer integrity [10].
• Expression of Rho mutant proteins in MDCK cells also altered levels of occludin serine/threonine phosphorylation, indicating that occludin is a target for Rho signaling [11].
• Furthermore, depletion of tight junction-localized occludin by an occludin extracellular domian peptide (20) correlated with a decrease in the HMW forms of occludin [12].

Other interactions of OCLN

• We also found that during the process of tight junction assembly after MEK1 inhibition, tyrosine phosphorylation of occludin and ZO-1, but not claudin-1, increased significantly [7].
• 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 [13].

Analytical, diagnostic and therapeutic context of OCLN

• Immunocytochemistry revealed that a pool of internalized occludin co-labels with the early endosome marker, EEA1, suggesting that PDGF may stimulate occludin to enter an endosomal pathway [14].
• Moreover, immunofluorescence labelling and confocal microscopy showed that ZO-1, but not occludin, around cell-cell boundaries was rearranged by HA/P treatment [1].
• Cell fractionation experiments with PDGF-treated cells revealed a novel occludin-containing low-density, detergent resistant subcellular structure, which increased in the buoyant fractions relative to occludin in the pellet in a time- and concentration-dependent manner [14].
• In addition, the distribution of the tight-junction-associated membrane proteins ZO-1 and occludin was analysed using immunofluorescence microscopy [15].
• Immunoblotting revealed that dispase fragmented occludin, whereas it remained unchanged in the intact urothelial cell sheets [16].

References