|TRPV4-KO cells show a delay in intercellular contact formation in response to extracellular Ca2+ induction compared with WT; stains are for actin (green), β-catenin (blue) and E-cadherin (red).
TRPV4 is a calcium channel that acts as a physiological sensor for stimuli such as heat, osmotic pressure and mechanical deformation. Skin keratinocytes are one of the cell types that express TRPV4. This is interesting because studies have shown that calcium signals can play a role in keratinocyte differentiation. Thus, TRPV4 and other TRP calcium channels might be involved. In this study, the researchers 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 remodeling was 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.
The TRPV4 Channel Contributes to Intercellular Junction Formation in Keratinocytes
Takaaki Sokabe, Tomoko Fukumi-Tominaga, Shigenobu Yonemura, Atsuko Mizuno and Makoto Tominaga
J. Biol. Chem., published online April 22, 2010
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