Occludin, a Constituent of Tight Junctions

Abstract

O ccludin was the first tight junction (TJ) integral membrane protein identified. This "65 kDa protein specifically localizes at TJs of epithelial and endothelial cells and is incorporated into the network of TJ strands. Occludin has a predicted tetraspan membrane topology with two extracellular loops and a large COOH-terminal cytoplasmic domain. Both extracellular domains are enriched with tyrosine residues, and in the first domain, more than half of the residues are tyrosines and glycines. Multiple domains of occludin are responsible for its localization and functions. Occludin interacts with many structural as well as signaling molecules and participates in the regulation of TJ functions. Although occludin-deficient mice show various phenotypes such as significant postnatal growth retardation, chronic inflammation, hyperplasia of the gastric epithelium, and calcification in the brain, the roles of occludin in vivo remain unclear since many epithelia in occludin null mice seem unaffected