Zyxin Antagonizes the FERM Protein Expanded to Couple F-Actin and Yorkie-Dependent Organ Growth
pmid: 25728696
Zyxin Antagonizes the FERM Protein Expanded to Couple F-Actin and Yorkie-Dependent Organ Growth
Coordinated multicellular growth during development is achieved by the sensing of spatial and nutritional boundaries. The conserved Hippo (Hpo) signaling pathway has been proposed to restrict tissue growth by perceiving mechanical constraints through actin cytoskeleton networks. The actin-associated LIM proteins Zyxin (Zyx) and Ajuba (Jub) have been linked to the control of tissue growth via regulation of Hpo signaling, but the study of Zyx has been hampered by a lack of genetic tools.We generated a zyx mutant in Drosophila using TALEN endonucleases and used this to show that Zyx antagonizes the FERM-domain protein Expanded (Ex) to control tissue growth, eye differentiation, and F-actin accumulation. Zyx membrane targeting promotes the interaction between the transcriptional co-activator Yorkie (Yki) and the transcription factor Scalloped (Sd), leading to activation of Yki target gene expression and promoting tissue growth. Finally, we show that Zyx's growth-promoting function is dependent on its interaction with the actin-associated protein Enabled (Ena) via a conserved LPPPP motif and is antagonized by Capping Protein (CP).Our results show that Zyx is a functional antagonist of Ex in growth control and establish a link between actin filament polymerization and Yki activity.
- Instituto Gulbenkian de Ciência Portugal
- Gulbenkian Institute for Molecular Medicine Portugal
- Cancer Research UK United Kingdom
- London Research Institute United Kingdom
Agricultural and Biological Sciences(all), Base Sequence, Biochemistry, Genetics and Molecular Biology(all), Organogenesis, Molecular Sequence Data, Membrane Proteins, Nuclear Proteins, Genes, Insect, DNA, Organ Size, Eye, Actins, Animals, Genetically Modified, Drosophila melanogaster, Amino Acid Substitution, Mutagenesis, Site-Directed, Trans-Activators, Animals, Drosophila Proteins, Female, Mutant Proteins, Amino Acid Sequence
Agricultural and Biological Sciences(all), Base Sequence, Biochemistry, Genetics and Molecular Biology(all), Organogenesis, Molecular Sequence Data, Membrane Proteins, Nuclear Proteins, Genes, Insect, DNA, Organ Size, Eye, Actins, Animals, Genetically Modified, Drosophila melanogaster, Amino Acid Substitution, Mutagenesis, Site-Directed, Trans-Activators, Animals, Drosophila Proteins, Female, Mutant Proteins, Amino Acid Sequence
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