Abstract
Transient receptor potential vanilloid 4 (TRPV4) channel is a physiological sensor for hypo-osmolarity, mechanical deformation, and warm temperature. The channel activation leads to various cellular effects involving Ca(2+) dynamics. We found that TRPV4 interacts with beta-catenin, a crucial component linking adherens junctions and the actin cytoskeleton, thereby enhancing cell-cell junction development and formation of the tight barrier between skin keratinocytes. TRPV4-deficient mice displayed impairment of the intercellular junction-dependent barrier function in the skin. In TRPV4-deficient keratinocytes, extracellular Ca(2+)-induced actin rearrangement and stratification were delayed following significant reduction in cytosolic Ca(2+) increase and small GTPase Rho activation. TRPV4 protein located where the cell-cell junctions are formed, and the channel deficiency caused abnormal cell-cell junction structures, resulting in higher intercellular permeability in vitro. Our results suggest a novel role for TRPV4 in the development and maturation of cell-cell junctions in epithelia of the skin.
Highlights
Transient receptor potential vanilloid 4 (TRPV4),3 a member of the TRP superfamily of cation channels, is a Ca2ϩ-permeable channel expressed in both neuronal and non-neuronal cells
The skin barrier function is achieved by keratinocytes in the epidermis, which consists of a basal layer and several differentiated layers covered with a cornified layer at the surface
We found the binding of TRPV4 and -catenin in both a heterologous expression system (Fig. 1C) and primary keratinocytes obtained from neonatal mice (Fig. 1D). -Catenin co-precipitated with TRPV4 was hardly observed in keratinocytes, which might be due to weak competency of the TRPV4 antibody for immunoprecipitation, relatively low expression level of TRPV4, or both
Summary
Transient receptor potential vanilloid 4 (TRPV4),3 a member of the TRP superfamily of cation channels, is a Ca2ϩ-permeable channel expressed in both neuronal and non-neuronal cells. Dye permeation increased more in TRPV4-deficient contact formation were clearly observed 4 h after the Ca2ϩ than in wild-type mice following acetone treatment (Fig. 2C, switch in wild-type cells, which was recognized by a single row acetone (ϩ)), suggesting that the cell-cell junction-dependent of E-cadherin immunoreactivity at sites of cell-cell contact
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