The deubiquitylating enzyme Fat Facets modulates Fat signalling and regulates tissue growth

Abstract

AbstractRegulation of tissue growth is influenced by many signals, including polarity cues. The Hippo signalling pathway restricts tissue growth and receives inputs from the planar cell polarity-controlling Fat signalling pathway. The atypical cadherin Fat restricts growth via several mechanisms that ultimately control the activity of the pro-growth transcriptional activator Yorkie. Fat signalling modulates the activity of the Yorkie inhibitory kinase Warts, as well as the function of the FERM protein Expanded, which promotes Hippo signalling and also directly inhibits Yorkie. Although several Fat pathway activity modulators are known to be involved in ubiquitylation, the role of this post-translational modification in the pathway remains unclear. Moreover, no deubiquitylating enzymes have been described in this pathway. Here, using anin vivoRNAi screening approach, we identify the deubiquitylating enzyme Fat facets as a regulator of Fat signalling that is important for tissue growth regulation. Fat facets interacts genetically and physically with Fat signalling components and regulates transcription of Yorkie target genes. Thus, we uncover a role for reversible ubiquitylation in the strict control of Fat signalling and, by extension, in the regulation of tissue growth.