Tricellulin regulates junctional tension of epithelial cells at tricellular contacts via Cdc42

Abstract

When the surface view of each epithelial cell is compared with a polygon, its sides correspond to cell–cell junctions, while its vertices correspond to tricellular contacts, whose roles in epithelial cell morphogenesis have not been well studied. Here, we show that tricellulin, which is localized at tricellular contacts, regulates F-actin organization via 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 a Cdc42 guanine nucleotide exchange factor, Tuba, and activates Cdc42. A tricellulin mutant that lacks the ability of Tuba binding 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.