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♦ See referenced article, J. Biol. Chem. 2010, 285, 18749–18758
TRPV4 is a calcium channel that acts as a physiological sensor for stimuli such as heat, osmotic pressure, and mechanical deformation. Among the cell types expressing TRPV4 are skin keratinocytes, which is interesting as studies have shown that calcium signals can play a role in keratinocyte differentiation. Thus TRPV4, and other TRP (transient receptor potential) calcium channels, might be involved. In this Paper of the Week, Takaaki Sokabe and colleagues found that TRPV4 interacts with β-catenin, the protein that links adherens junctions to the actin cytoskeleton and a critical component of skin as it promotes the tight barrier between skin cells. In cell studies, they found that TRPV4 localized to where cell-cell junctions are formed and TRPV4 deficiency resulted in abnormal cell-cell junction structures and higher intercellular permeability. In vivo, this translated to TRPV4-deficient mice displaying impaired intercellular junction-dependent barrier function in their skin. In TRPV4-deficient keratinocytes, extracellular Ca2+-induced actin rearrangement and stratification were both delayed, which was accompanied by a significant reduction in the activation of the small GTPase Rho, a key regulator of keratinocyte differentiation. Together, the results of this study suggest a novel role for TRPV4 in the development and maturation of cell-cell junctions in the skin, indicating a critical role in maintaining skin integrity.