Spectrin regulates Hippo signaling by modulating cortical actomyosin activity

• Published in: eLife 2015-03, Vol.4, p.e06567-e06567
• Main Authors: Deng, Hua, Wang, Wei, Yu, Jianzhong, Zheng, Yonggang, Qing, Yun, Pan, Duojia
• Format: Article
• Language: English
• Subjects: Actin Cytoskeleton - genetics; Actin Cytoskeleton - metabolism; Actin Cytoskeleton - ultrastructure; Actomyosin; Actomyosin - genetics; Actomyosin - metabolism; Animals; Cell adhesion & migration; Cell Biology; cell tension; Cloning; Cortex; Cytoskeleton; Developmental Biology and Stem Cells; Drosophila; Drosophila melanogaster - cytology; Drosophila melanogaster - genetics; Drosophila melanogaster - growth & development; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Eye - cytology; Eye - growth & development; Eye - metabolism; Female; Gene Expression Regulation, Developmental; Genes, Reporter; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Imaginal Discs - growth & development; Imaginal Discs - metabolism; Imaginal Discs - ultrastructure; Inhibitor of Apoptosis Proteins - genetics; Inhibitor of Apoptosis Proteins - metabolism; Insects; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Kinases; Mechanical stimuli; Membrane proteins; Mitosis; Muscle contraction; Myosin; myosin activity; Neurofibromin 2; organ size; Ovarian Follicle - growth & development; Ovarian Follicle - metabolism; Ovarian Follicle - ultrastructure; Phosphorylation; Plasma; Primary Cell Culture; Protein Isoforms - genetics; Protein Isoforms - metabolism; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proteins; Pupa - cytology; Pupa - genetics; Pupa - growth & development; Pupa - metabolism; Regulation; Signal Transduction; Spectrin; Spectrin - genetics; Spectrin - metabolism; Transcription; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.06567

The Hippo pathway controls tissue growth through a core kinase cascade that impinges on the transcription of growth-regulatory genes. Understanding how this pathway is regulated in development remains a major challenge. Recent studies suggested that Hippo signaling can be modulated by cytoskeletal tension through a Rok-myosin II pathway. How cytoskeletal tension is regulated or its relationship to the other known upstream regulators of the Hippo pathway remains poorly defined. In this study, we identify spectrin, a contractile protein at the cytoskeleton-membrane interface, as an upstream regulator of the Hippo signaling pathway. We show that, in contrast to canonical upstream regulators such as Crumbs, Kibra, Expanded, and Merlin, spectrin regulates Hippo signaling in a distinct way by modulating cortical actomyosin activity through non-muscle myosin II. These results uncover an essential mediator of Hippo signaling by cytoskeleton tension, providing a new entry point to dissecting how mechanical signals regulate Hippo signaling in living tissues.