Yorkie Functions at the Cell Cortex to Promote Myosin Activation in a Non-transcriptional Manner

Abstract

The Hippo signaling pathway is an evolutionarily conserved mechanism that controls organ size in animals. Yorkie is well known as a transcriptional co-activator that functions downstream of the Hippo pathway to positively regulate transcription of genes that promote tissue growth. Recent studies have shown that increased myosin activity activates both Yorkie and its vertebrate orthologue YAP, resulting in increased nuclear localization and tissue growth. Here we show that Yorkie also can accumulate at the cell cortex in the apical junctional region. Moreover, Yorkie functions at the cortex to promote activation of myosin through a myosin regulatory light chain kinase, Stretchin-Mlck. This Yorkie function is not dependent on its transcriptional activity and is required for larval and adult tissues to achieve appropriate size. Based on these results, we suggest that Yorkie functions in a feedforward "amplifier" loop that promotes myosin activation, and thereby greater Yorkie activity, in response to tension.

Yorkie controls tube length and apical barrier integrity in the developingDrosophilaairways

“…12A). These findings together with previous observations in wing imaginal disc (Xu et al, 2018) point to a transcription-independent role of Yki in the apical cell cortex to regulate the apical cytoskeleton. Second, residual Yki molecules, which do not bind Tsr, are free to translocate to the nucleus and transcribe Alas to regulate crosslinking of cuticular proteins, and genes involved in in tissue size regulation, such as diap1 (Fig.…”

Mechanical Force-Driven Adherens Junction Remodeling and Epithelial Dynamics

“…Upon cortical tension increase and Yorkie activation, this transcriptional co-activator promotes cell growth, proliferation, and tension decrease (Pan et al, 2016). Lastly, recent work reported that cortical Yki can also promote Myo activation in a transcriptional-independent manner (Xu et al, 2018). New Role for Wnt/b-Cat Signaling in Epithelial Tissue Mechanosensing b-cat, a core component of the cadherin adhesive complex, is able to respond to Wnt ligands and act as a transcriptional coactivator.…”

Growth control in the Drosophila wing disk

“…Feedback loops through Yki, such as a short one through dmyc (Neto‐Silva, de Beco, & Johnston, ), can serve to limit Yki signaling, while other feedback targets include crumbs , ds , expanded , merlin , wts , kibra , and four‐jointed ( fj ) (Cho et al, ; Enderle & McNeill, ; Fulford, Tapon, & Ribeiro, ; Ikmi et al, ; Irvine, ; Nolo, Morrison, Tao, Zhang, & Halder, ; Oh & Irvine, ; Wang, Zhang, & Blair, ; Wartlick, Mumcu, Jülicher, & Gonzalez‐Gaitan, ; Zecca & Struhl, ). In addition, Yki modulates morphogen signaling by transcriptional control of the glypicans dally and dlp —which encode co‐receptors or sequestering proteins for Dpp and Wg (Baena‐Lopez, Rodríguez, & Baonza, ; Fujise et al, ; Kreuger et al, )—and Yki also activates myosin at the membrane (Xu et al, ). Following establishment of the DV boundary there are four compartments in the wing pouch, each of which evolves independently to a certain degree.…”