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ZO-1 forms complexes with either ZO-2 or ZO-3. In addition, these proteins can also associate with claudin, occludin and F-actin, at tight junction stands, where they provide a linkage between the actin cytoskeleton and the tight junction. ZO-1 expression is significantly reduced in many breast cancer lines. ZO-2 and ZO-3 are ubiquitously expressed within epithelial tight junctions, and unlike ZO-1, which is also expressed at cell junctions of cardiac myocytes, ZO-2 is not expressed in nonepithelial tissue. ZO-1 is a protein located on a cytoplasmic membrane surface of intercellular tight junctions. ZO-1 may be involved in signal transduction at cell-cell junctions. Two transcript variants encoding distinct isoforms have been identified for the ZO-1 gene. Diseases associated with ZO-1 dysfunction include Celiac Disease and Congenital Nephrotic Syndrome.
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