The mechanosensitive protein Zyxin influences Hippo signaling and tissue growth via adherens junctions and basal spot junctions in Drosophila.

Abstract

Mechanical forces such as tension and compression play a central role in the growth and morphogenesis of tissues. Cell-cell junctions and the actin cytoskeleton are key mediators of mechanical forces and influence the activity of signaling networks, including the Hippo pathway. Here, we show that the mechanosensitive protein Zyxin (Zyx) localizes predominantly to adherens junctions (AJs) and basal spot junctions (BSJs) of Drosophila epithelial tissues. At these subcellular locations, Zyx works in concert with Ajuba to limit Hpo signaling and promote Drosophila epithelial tissue growth. Zyx recruits both Ajuba and the central Hpo pathway kinase Warts (Wts) to AJs and BSJs, which likely limits Wts activity by segregating it from Hpo pathway activator proteins. We further show that Zyx's association with cell-cell junctions is promoted by cytoskeletal tension and that Zyx supports the transmission of actomyosin tension to AJs in growing epithelial tissues. These findings indicate the conservation of this function. Thus, we provide new insights into how Zyx couples mechanical cues to Hpo pathway-dependent tissue growth and highlight the importance of BSJs and their associated actomyosin network in epithelial tissue development.