The TRPV4 cation channel: A molecule linking skin temperature and barrier function.

The skin barrier function is indispensable for terrestrial animals to avoid dehydration. The function is achieved by a hydrophobic cornified layer consisting of dead keratinocytes and lipids, and by an intercellular junction barrier formed among differentiated keratinocytes. A recent report demonstrated that TRPV4, one of the temperature-sensitive cation channels, contributes to the formation and maintenance of the intercellular junction-dependent barrier in the skin. TRPV4 associates with the E-cadherin complex via β-catenin, and thereby participates in the promotion of cell-cell junction development. TRPV4 allows influx of Ca(2+) ions from the extracellular space at physiological skin temperatures. The Ca(2+) influx induces Rho activation and promotes actin fiber organization and junction formation, thereby augmenting barrier integrity. Indeed, the intercellular junction structures and the skin barrier function were impaired in TRPV4-deficeint mice. This novel role of TRPV4 in keratinocytes may explain the significant correlation between temperature and the condition of skin.>