Disease relevance of Cldn3

• Clostridium perfringens enterotoxin (CPE), a single approximately 35-kD polypeptide, was reported to specifically bind to claudin-3/RVP1 and claudin-4/CPE-R at its COOH-terminal half [1].
• CONCLUSIONS.: Claudin-3 and claudin-4 receptors may offer promising targets for the use of CPE as a novel type-specific therapy against this highly aggressive and chemotherapy-resistant variant of endometrial cancer [2].
• Finally, the in vivo therapeutic effect of sublethal doses of CPE was studied in SCID mouse xenografts harboring subcutaneous and intraperitoneal USPC that expressed claudin-3 and claudin-4 [2].

High impact information on Cldn3

• 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 [3].
• C-CPE bound to claudin-3 and -4 with high affinity, but not to claudin-1 or -2 [1].
• Sertoli cell-specific ablation of androgen receptor results in increased permeability of the blood-testis barrier to biotin, suggesting claudin 3 regulates the movement of small molecules across the Sertoli cell tight junctions [4].
• We show that testosterone, acting through its receptor expressed in Sertoli cells, regulates the expression of claudin 3, which encodes a transient component of newly formed tight junctions [4].
• Clostridium perfringens enterotoxin elicits rapid and specific cytolysis of breast carcinoma cells mediated through tight junction proteins claudin 3 and 4 [5].

Biological context of Cldn3

• To observe TJs in live epithelial cellular sheets, green fluorescent protein (GFP) was fused to the N-terminus of claudin-3 (a major cell adhesion molecule of TJs), which was stably expressed at a level that was approximately 50% of that of endogenous claudin-3 in mouse Eph4 epithelial cells [6].
• Using gene expression profiling, we recently identified high expression of the claudin-3 and claudin-4 receptors in a limited set of USPC [2].
• The mouse homologs Cpetr1 and Cpetr2 were identified and mapped to the conserved syntenic region on mouse chromosome 5 [7].

Anatomical context of Cldn3

• Data obtained by reverse transcriptase-polymerase chain reaction, Western blot, and immunofluorescence microscopy showed the expression and localization of claudin-3 to -8, -10, and -11 at epithelial tight junctions [8].
• Claudin-3, -5, and -7 were expressed in all of the luminal epithelial cells of the ducts at all of the developmental stages examined and in those of terminal tubules at E16 and later [8].
• We constructed claudin-1/claudin-3 chimeric molecules and found that the second extracellular loop of claudin-3 conferred CPE sensitivity on L fibroblasts [9].

Associations of Cldn3 with chemical compounds

• METHODS.: Claudin-3 and claudin-4 receptor expression was analyzed at the mRNA and protein levels in flash-frozen and formalin-fixed, paraffin-embedded tissue from 20 consecutive USPC patients [2].

Other interactions of Cldn3

• Gene array experiments, together with protein expression analysis by immunoblotting, revealed a differential spatiotemporal distribution of several proteins associated with epithelial maturation and polarization, including intercellular junctional proteins (e.g., ZO-1, claudin-3, E-cadherin) and the subapical cytoskeletal/microvillar protein ezrin [10].
• In the acini-like terminal buds of the treated glands, tight junction proteins of ZO-1 and claudin-3 delineated the lumen and the apical membrane protein aquaporin-5 accumulated at the luminal cell surfaces [11].

Analytical, diagnostic and therapeutic context of Cldn3

• Immunofluorescence and immunoelectron microscopy with polyclonal antibodies specific for claudin-3, -4, or -8 revealed that these molecules were exclusively concentrated at TJs in the liver and/or kidney [12].

References