Biology subjects

Ribeiro, P. S.

Publications and source records attributed to Ribeiro, P. S..

3 recordsLinked to original sources

bioRxiv2024

A Dual Role for the PP2A Phosphatase in Hippo Signalling Regulation

Hippo signalling is an evolutionarily conserved pathway that regulates tissue growth. The FERM domain protein Expanded plays a crucial role in integrating polarity cues to activate the Hippo pathway. Previous work has shown that the apicobasal polarity protein Crumbs can limit Hippo activity by promoting the phosphorylation and degradation of Expanded. Here, we provide evidence that PP2AWrd can counteract the effects of Crumbs, by dephosphorylating and stabilising Expanded. Indeed, we demonstrate that the PP2AWrd holoenzyme can increase Hippo signalling activity, in contrast to the previously established Hippo pathway inhibitory role of the PP2ACka-containing STRIPAK complex. We also uncover a role for PP2AWrd and PP2ATws in the regulation of Expanded proteostasis. Remarkably, the upstream Hippo regulator, Kibra interacts with PP2AWrd and prevents Expanded degradation. However, Kibra is unable to antagonise Crumbs-mediated Expanded regulation, in agreement with the previously established role of Crumbs in inhibiting Kibra function. Overall, our work characterises a novel Hippo-activating role for PP2A in the stabilisation of Expanded and provides new insights into how PP2A tightly controls Hippo activity in response to polarity stimuli.

developmental biology↗

bioRxiv2024

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

Tissue growth is regulated 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 co-activator Yorkie. The Fat pathway 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 an in vivo RNAi screening approach, we identify the deubiquitylating enzyme Fat facets as a positive regulator of Fat signalling that is important for tissue growth control. 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 control of Fat signalling and, by extension, in the regulation of tissue growth.

developmental biology↗

bioRxiv2020

drICE restrains DIAP2-mediated inflammatory signalling and intestinal inflammation

The Drosophila IAP protein, DIAP2, is a key mediator of NF-κB signalling and is required for immune activation, both locally in the intestinal epithelia and during systemic, fat body-induced responses. We have found that transgenic expression of DIAP2 induces inflammation in the intestine, but not in the fat body, indicating a need for regulating DIAP2 in microbiotic environments. We describe the Drosophila caspase drICE, a known interaction partner of DIAP2, as a regulator of DIAP2 and NF-κB signalling in the intestinal epithelium. drICE acts by cleaving, and interfering with DIAP2’s ability to ubiquitinate and, thereby, activate mediators of the NF-κB pathway. The drICE-cleaved form of DIAP2 is, moreover, unable to induce inflammation during basal conditions in the intestine. Interestingly, cleavage of DIAP2 does not interfere with pathogen-induced signalling, suggesting that drICE protects from immune responses induced by resident microbes. Accordingly, the negative regulatory effect of drICE is lost when rearing flies axenic. Hence, we show that drICE halts unwanted inflammatory signalling in the intestine by forming an inhibitory complex with DIAP2, interfering with the ability of DIAP2 to induce downstream signalling and NF-κB target gene activation.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cell biology↗