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.

Keywords: Hippo pathway; Stretchin-Mlck; Yorkie; apical junctional region; growth control; myosin; positive feedback.