The role of claudins in determining paracellular charge selectivity

Tight junctions create regulated barriers in the paracellular space between epithelial cells, including those of the airway and alveolus. Junctions vary widely throughout the body in their electrical resistance and, to some extent, in their ionic charge selectivity. Paracellular differences complement transcellular transport to define overall water, ion, and solute movements. A large family of transmembrane proteins called claudins has recently been implicated in creating the variable properties of the junction. Here we highlight the evidence that claudins are functional components of the barrier. Supportive data include evidence from deletion of selected claudins in mice, human genetic diseases of claudins 14 and 16, and direct experimental tests of the hypothesis that the extracellular charged residues on claudins influence the passage of ions through the junction. Alterations in claudin expression profiles may contribute to epithelial lung dysfunction during infection and inflammation. Much work remains to be done in the molecular characterization of tight junctions in the lung in normal physiology and during pathologic processes.