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Modulating F-actin organization induces organ growth by affecting the Hippo pathway
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Journal Article
Modulating F-actin organization induces organ growth by affecting the Hippo pathway
2011
Overview
The Hippo tumour suppressor pathway is a conserved signalling pathway that controls organ size. The core of the Hpo pathway is a kinase cascade, which in
Drosophila
involves the Hpo and Warts kinases that negatively regulate the activity of the transcriptional coactivator Yorkie. Although several additional components of the Hippo pathway have been discovered, the inputs that regulate Hippo signalling are not fully understood. Here, we report that induction of extra F‐actin formation, by loss of Capping proteins A or B, or caused by overexpression of an activated version of the formin Diaphanous, induced strong overgrowth in
Drosophila
imaginal discs through modulating the activity of the Hippo pathway. Importantly, loss of Capping proteins and Diaphanous overexpression did not significantly affect cell polarity and other signalling pathways, including Hedgehog and Decapentaplegic signalling. The interaction between F‐actin and Hpo signalling is evolutionarily conserved, as the activity of the mammalian Yorkie‐orthologue Yap is modulated by changes in F‐actin. Thus, regulators of F‐actin, and in particular Capping proteins, are essential for proper growth control by affecting Hippo signalling.
This study identifies actin organization as an upstream regulator of the Hippo pathway: F‐actin accumulation promotes Yorkie‐dependent transcriptional activation. This modulation of Hippo signalling by actin regulators controls organ growth in Drosophila.
Publisher
John Wiley & Sons, Ltd,Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ Animals
/ Carrier Proteins - biosynthesis
/ Drosophila melanogaster - chemistry
/ Drosophila melanogaster - cytology
/ Drosophila melanogaster - genetics
/ Drosophila Proteins - biosynthesis
/ Drosophila Proteins - chemistry
/ Drosophila Proteins - genetics
/ EMBO05
/ EMBO11
/ F-actin
/ Formins
/ Humans
/ Intracellular Signaling Peptides and Proteins - chemistry
/ Intracellular Signaling Peptides and Proteins - genetics
/ Organ Specificity - genetics
/ Protein Serine-Threonine Kinases - chemistry
/ Protein Serine-Threonine Kinases - genetics
/ Proteins
/ RNA Caps - antagonists & inhibitors
/ Signal Transduction - genetics
/ Tumor Suppressor Proteins - chemistry
/ Tumor Suppressor Proteins - genetics
/ Tumors
