Epithelial cells develop tight junctions (TJs) and cell polarity. Both properties are sensitive to environmental signals such as the epidermal growth factor (EGF) and the cardiotonic steroid ouabain. EGF is regarded as the main protector against injuries in epithelia, and ouabain is a hormone that regulates blood pressure, natriuresis, cell survival, and cell adhesion. After treatment with epidermal growth factor or ouabain, epithelial dog kidney MDCK cells undergo a drastic remodeling that includes changes in the transcription, translation, localization, and degradation of cell junction proteins. Degradation of these proteins involves selective and nonselective autophagy as well as endocytic lysosomal and proteasomal routes. The remodeling mechanism of tight junction’s proteins includes the activation of Src and ERK1/ERK2 kinases, the phosphorylation and translocation into the nucleus of the transcription factor STAT3, the activation of PKC to induce the endocytosis of claudin-2, and the delivery of this protein to the lysosomes. Whole communicating junctions and desmosomes are internalized by one cell and sent to degradation by nonselective autophagy. Nonselective and selective autophagies in epithelial cells are very context dependent; nevertheless, it is clear that, together with endocytic lysosomal and proteasomal degradation, they play a key role in the remodeling and functioning of cell junctions.
Part of the book: Lysosomes