title: Modulating F-actin organization induces organ growth by affecting the Hippo pathway.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Leticia
authors.initials: L
authors.lastname: Sansores-Garcia
authors.forename: Wouter
authors.initials: W
authors.lastname: Bossuyt
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Wada
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yonemura
authors.forename: Chunyao
authors.initials: C
authors.lastname: Tao
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Georg
authors.initials: G
authors.lastname: Halder
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000737:chemistry / Q000235:genetics; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D004331:Drosophila melanogaster / Q000737:chemistry / Q000166:cytology / Q000235:genetics; D000080865:Formins; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics*; D012315:RNA Caps / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics; D014921:Wings, Animal / Q000737:chemistry / Q000166:cytology* / Q000254:growth & development*; D000099317:Hippo Kinases
chemical_list: D000199:Actins; D002352:Carrier Proteins; D029721:Drosophila Proteins; D000080865:Formins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D012315:RNA Caps; D025521:Tumor Suppressor Proteins; C106890:diaphanous protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases