Cytoskeletal Tension Inhibits Hippo Signaling through an Ajuba-Warts Complex
Cytoskeletal Tension Inhibits Hippo Signaling through an Ajuba-Warts Complex
Mechanical forces have been proposed to modulate organ growth, but a molecular mechanism that links them to growth regulation in vivo has been lacking. We report that increasing tension within the cytoskeleton increases Drosophila wing growth, whereas decreasing cytoskeletal tension decreases wing growth. These changes in growth can be accounted for by changes in the activity of Yorkie, a transcription factor regulated by the Hippo pathway. The influence of myosin activity on Yorkie depends genetically on the Ajuba LIM protein Jub, a negative regulator of Warts within the Hippo pathway. We further show that Jub associates with α-catenin and that its localization to adherens junctions and association with α-catenin are promoted by cytoskeletal tension. Jub recruits Warts to junctions in a tension-dependent manner. Our observations delineate a mechanism that links cytoskeletal tension to regulation of Hippo pathway activity, providing a molecular understanding of how mechanical forces can modulate organ growth.
- Rutgers, The State University of New Jersey United States
- Howard Hughes Medical Institute United States
Biochemistry, Genetics and Molecular Biology(all), Intracellular Signaling Peptides and Proteins, Nuclear Proteins, YAP-Signaling Proteins, LIM Domain Proteins, Protein Serine-Threonine Kinases, Biomechanical Phenomena, Trans-Activators, Animals, Drosophila Proteins, Wings, Animal, Drosophila, Cytoskeleton, Signal Transduction
Biochemistry, Genetics and Molecular Biology(all), Intracellular Signaling Peptides and Proteins, Nuclear Proteins, YAP-Signaling Proteins, LIM Domain Proteins, Protein Serine-Threonine Kinases, Biomechanical Phenomena, Trans-Activators, Animals, Drosophila Proteins, Wings, Animal, Drosophila, Cytoskeleton, Signal Transduction
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