title: The TRPV4 channel contributes to intercellular junction formation in keratinocytes.
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.
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki 444-8787, Japan. sokabe@nips.ac.jp
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sokabe
authors.forename: Tomoko
authors.initials: T
authors.lastname: Fukumi-Tominaga
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yonemura
authors.forename: Atsuko
authors.initials: A
authors.lastname: Mizuno
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002450:Cell Communication; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D007365:Intercellular Junctions / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008954:Models, Biological; D009994:Osmolar Concentration; D050916:TRPV Cation Channels / Q000378:metabolism*; D013696:Temperature; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000199:Actins; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; D051176:beta Catenin; D002118:Calcium