The roles of claudin superfamily proteins in paracellular transport

The claudin superfamily consists of at least 18 homologous proteins in huma ns. These proteins are important structural and functional components of ti ght junctions in paracellular transport. Complexed with two other integral transmembrane proteins, occludin and junctional adhesion molecule, claudins are located in both epithelial and endothelial cells in all tight junction -bearing tissues. Claudins interact directly with tight junction-specific, membrane-associated guanylate kinase homologues, ZO-1, ZO-2, and ZO-3, and indirectly with AF-6 and the myosin-binding molecule cingulin. These protei n-protein interactions promote scaffolding of the tight junction transmembr ane proteins and provide a link to the actin cytoskeleton for transducing r egulatory signals to and from tight junctions. The distinct permeability pr operties observed in different epithelia and endothelia seemingly result fr om the restricted tissue expression, variability of the homopolymer and het eropolymer assembly, regulated transcription and translation, and the subce llular localization of claudin family proteins. Defects in claudins are cau satively associated with a variety of human diseases, demonstrating that cl audins play important roles in human physiology. In conditions where the ce ll adhesion function contributed by tight junctions is essential, such as i n altered paracellular transport, in proliferative diseases, and during mor phogenesis, the claudin superfamily of homologous proteins provides the mol ecular basis for the uniqueness of tight junctions and emerges as a new tar get for intervention.