title: Fluid shear triggers microvilli formation via mechanosensitive activation of TRPV6.
abstract: Microvilli are cellular membrane protrusions present on differentiated epithelial cells, which can sense and interact with the surrounding fluid environment. Biochemical and genetic approaches have identified a set of factors involved in microvilli formation; however, the underlying extrinsic regulatory mechanism of microvilli formation remains largely unknown. Here we demonstrate that fluid shear stress (FSS), an external mechanical cue, serves as a trigger for microvilli formation in human placental trophoblastic cells. We further reveal that the transient receptor potential, vanilloid family type-6 (TRPV6) calcium ion channel plays a critical role in flow-induced Ca(2+) influx and microvilli formation. TRPV6 regulates phosphorylation of Ezrin via a Ca(2+)-dependent phosphorylation of Akt; this molecular event is necessary for microvillar localization of Ezrin in response to FSS. Our findings provide molecular insight into the microvilli-mediated mechanoresponsive cellular functions, such as epithelial absorption, signal perception and mechanotransduction.
authors.affiliation: Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan.|Takeuchi Biohybrid Innovation Project, Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology (JST), Tokyo 153-8904, Japan.
authors.forename: Shigenori
authors.initials: S
authors.lastname: Miura
authors.affiliation: Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan.|Takeuchi Biohybrid Innovation Project, Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology (JST), Tokyo 153-8904, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Sato
authors.affiliation: Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan.|Takeuchi Biohybrid Innovation Project, Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology (JST), Tokyo 153-8904, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Kato-Negishi
authors.affiliation: Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan.
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Teshima
authors.affiliation: Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan.|Takeuchi Biohybrid Innovation Project, Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology (JST), Tokyo 153-8904, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Takeuchi
mesh_terms: D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D040542:Mechanotransduction, Cellular; D008871:Microvilli / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism; D000099149:Ezrin
chemical_list: D002118:Calcium; D015220:Calcium Channels; D003598:Cytoskeletal Proteins; D050916:TRPV Cation Channels; D000099149:Ezrin; C422827:TRPV6 protein, human