RRC ID 15541
Author Fernández BG, Gaspar P, Brás-Pereira C, Jezowska B, Rebelo SR, Janody F.
Title Actin-Capping Protein and the Hippo pathway regulate F-actin and tissue growth in Drosophila.
Journal Development
Abstract The conserved Hippo tumor suppressor pathway is a key kinase cascade that controls tissue growth by regulating the nuclear import and activity of the transcription co-activator Yorkie. Here, we report that the actin-Capping Protein αβ heterodimer, which regulates actin polymerization, also functions to suppress inappropriate tissue growth by inhibiting Yorkie activity. Loss of Capping Protein activity results in abnormal accumulation of apical F-actin, reduced Hippo pathway activity and the ectopic expression of several Yorkie target genes that promote cell survival and proliferation. Reduction of two other actin-regulatory proteins, Cofilin and the cyclase-associated protein Capulet, cause abnormal F-actin accumulation, but only the loss of Capulet, like that of Capping Protein, induces ectopic Yorkie activity. Interestingly, F-actin also accumulates abnormally when Hippo pathway activity is reduced or abolished, independently of Yorkie activity, whereas overexpression of the Hippo pathway component expanded can partially reverse the abnormal accumulation of F-actin in cells depleted for Capping Protein. Taken together, these findings indicate a novel interplay between Hippo pathway activity and actin filament dynamics that is essential for normal growth control.
Volume 138(11)
Pages 2337-46
Published 2011-6-1
DOI 10.1242/dev.063545
PII dev.063545
PMID 21525075
MeSH Actin Capping Proteins / metabolism* Actin Depolymerizing Factors / deficiency Actins / metabolism* Animals Blotting, Western Cell Proliferation Drosophila / growth & development* Drosophila / metabolism Drosophila Proteins / deficiency Drosophila Proteins / genetics Drosophila Proteins / metabolism* Gene Expression Regulation, Developmental Intracellular Signaling Peptides and Proteins / deficiency Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* Microfilament Proteins / deficiency Nuclear Proteins / metabolism* Polymerase Chain Reaction Protein Serine-Threonine Kinases / deficiency Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* Signal Transduction Trans-Activators / metabolism* Wings, Animal / growth & development Wings, Animal / metabolism YAP-Signaling Proteins
IF 5.611
Times Cited 194
WOS Category DEVELOPMENTAL BIOLOGY
Resource
Drosophila 4005R-2 5061R-2 12072R-1