Significance: ZO-1, ZO-2, and ZO-3 are scaffold proteins of the tight junction (TJ) that belong to the MAGUK protein family characterized for exhibiting PDZ, SH3, and GuK domains. ZO proteins are present only in multicellular organisms, being the placozoa the first to have them. ZO proteins associate among themselves and with other integral and adaptor proteins of the TJ, of the ZA and of gap junctions, as with numerous signaling proteins and the actin cytoskeleton. ZO proteins are also present at the nucleus of proliferating cells.
Recent advances: Oxidative stress disassembles the TJs of endothelial and epithelial cells.
Critical issues: Oxidative stress alters ZO proteins expression and localization, in conditions like hypoxia, bacterial and viral infections, vitamin deficiencies, age-related diseases, diabetes and inflammation, alcohol and tobacco consumption.
Future directions: Molecules present in the signaling pathways triggered by oxidative stress can be targets for therapeutic intervention.