title: Tricellulin regulates junctional tension of epithelial cells at tricellular contacts through Cdc42.
abstract: When the surface view of each epithelial cell is compared with a polygon, its sides correspond to cell-cell junctions, whereas its vertices correspond to tricellular contacts, whose roles in epithelial cell morphogenesis have not been well studied. Here, we show that tricellulin (also known as MARVELD2), which is localized at tricellular contacts, regulates F-actin organization through Cdc42. Tricellulin-knockdown epithelial cells exhibit irregular polygonal shapes with curved cell borders and impaired organization of F-actin fibers around tricellular contacts during cell-cell junction formation. The N-terminal cytoplasmic domain of tricellulin binds to the Cdc42 guanine-nucleotide-exchange factor (GEF) Tuba (also known as DNMBP and ARHGEF36), and activates Cdc42. A tricellulin mutant that lacks the ability to bind Tuba cannot rescue the curved cell border phenotype of tricellulin-knockdown cells. These findings indicate that tricellular contacts play crucial roles in regulating the actomyosin-mediated apical junctional complex tension through the tricellulin-Tuba-Cdc42 system.
authors.affiliation: Division of Cell Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Yukako
authors.initials: Y
authors.lastname: Oda
authors.affiliation: Laboratory for Morphogenetic Signaling, RIKEN Center for Developmental Biology, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Tetsuhisa
authors.initials: T
authors.lastname: Otani
authors.affiliation: Department of Biology, Faculty of Sciences, Kyushu University, Kyushu, 812-8581, Japan PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Ikenouchi
authors.affiliation: Division of Cell Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan Division of Cerebral Structure, National Institute for Physiological Sciences, Okazaki 444-8787, Japan Department of Physiological Sciences, The Graduate School for Advanced Studies, Okazaki 444-8585, Japan furuse@nips.ac.jp.
authors.forename: Mikio
authors.initials: M
authors.lastname: Furuse
mesh_terms: D018938:Caco-2 Cells; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D062794:MARVEL Domain Containing 2 Protein / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism*
chemical_list: D062794:MARVEL Domain Containing 2 Protein; D020764:cdc42 GTP-Binding Protein
keywords: Cdc42; Cell–cell junction; Epithelial cell; F-actin; MARVELD2; Tricellulin; Tuba