Epithelial paracellular proteins in health and disease

Tight junctions are intercellular seams sealing and preventing the entrance of microorganisms or unwanted substances from the luminal compartment. They also define the border between the basolateral and apical membranes of polarized cells, thus enabling the normal transcellular vectorial transport typical of epithelial function. Their major components are claudin and occludin proteins. Tight junctions are now recognized as having more specific properties in cell function. This review will concentrate on novel findings related to tight junctions in polarized cells.

Tight junctions are regulated, interacting with the cell cytoskeleton and being responsible for the reabsorption of molecules. The latter has been exemplified by the discovery of claudin 16 (paracellin-1) as the gene product responsible for the hypomagnesaemia with hypercalciuria syndrome. Pathogenic bacteria and viruses target and use the tight-junction machinery to invade multicellular organisms.

Tight-junction-targeted research may help not only in the future design of novel therapies against invading microorganisms, but also may promote passage of medications through the normally sealed epithelial barrier. In addition, the regulatory properties of tight junctions may help in the understanding of still unanswered aspects of epithelial ion transport.