Modulating F-actin organization induces organ growth by affecting the Hippo pathway

EMBO J. 2011 May 10;30(12):2325-35. doi: 10.1038/emboj.2011.157.

Abstract

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.

MeSH terms

  • Actins / biosynthesis
  • Actins / chemistry
  • Actins / genetics*
  • Animals
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics
  • Cell Proliferation
  • Cells, Cultured
  • Cytoskeleton / chemistry
  • Cytoskeleton / genetics
  • Drosophila Proteins / biosynthesis
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics*
  • Drosophila melanogaster / chemistry
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics
  • Formins
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Organ Specificity / genetics
  • Phenotype
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / genetics*
  • RNA Caps / antagonists & inhibitors
  • RNA Caps / chemistry
  • RNA Caps / genetics
  • Signal Transduction / genetics*
  • Tumor Suppressor Proteins / chemistry
  • Tumor Suppressor Proteins / genetics
  • Wings, Animal / chemistry
  • Wings, Animal / cytology*
  • Wings, Animal / growth & development*

Substances

  • Actins
  • Carrier Proteins
  • Drosophila Proteins
  • Formins
  • Intracellular Signaling Peptides and Proteins
  • RNA Caps
  • Tumor Suppressor Proteins
  • diaphanous protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • hpo protein, Drosophila