Channel functions of claudins in the organization of biological systems

Claudins are tight junction proteins mostly appreciated in their function of paracellular barrier-formation. Compared to a virtual absence of any tight junctions, their paracellular sealing role certainly stands out. Yet, it was recognized immediately after the discovery of the first claudins, that some members of the claudin protein family were able to convey size and charge selectivity to the paracellular pathway. Thus, paracellular permeability can be fine-tuned according to the physiological needs of a tissue by inserting these channel-forming claudins into tight junction strands. Precise permeability adjustment is further suggested by the presence of numerous isoforms of channel-forming claudins (claudin-10b-, -15-, -16-like isoforms) in various vertebrate taxa. Moreover, their expression and localization are controlled by multiple transcriptional and posttranslational mechanisms. Consequently, mutation or dysregulation of channel-forming claudins can cause severe diseases. The present review therefore aims at providing an up-to-date report of the current research on these aspects of channel-forming claudins and their possible implications on future developments.