title: Spectrin regulates Hippo signaling by modulating cortical actomyosin activity.
abstract: 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.
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Hua
authors.initials: H
authors.lastname: Deng
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Yun
authors.initials: Y
authors.lastname: Qing
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Duojia
authors.initials: D
authors.lastname: Pan
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D000205:Actomyosin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D005123:Eye / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D060227:Imaginal Discs / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D006080:Ovarian Follicle / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D061251:Primary Cell Culture; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011679:Pupa / Q000166:cytology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D015398:Signal Transduction; D013049:Spectrin / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000099317:Hippo Kinases
chemical_list: D000205:Actomyosin; D029721:Drosophila Proteins; D049452:Green Fluorescent Proteins; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases; D013049:Spectrin; D025521:Tumor Suppressor Proteins; C111891:DIAP1 protein, Drosophila; C548168:kibra protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases
keywords: D. melanogaster; cell biology; cell tension; cytoskeleton; developmental biology; myosin activity; organ size; signal transduction; stem cells
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