title: The Hippo pathway polarizes the actin cytoskeleton during collective migration of Drosophila border cells.
abstract: Collective migration of Drosophila border cells depends on a dynamic actin cytoskeleton that is highly polarized such that it concentrates around the outer rim of the migrating cluster of cells. How the actin cytoskeleton becomes polarized in these cells to enable collective movement remains unknown. Here we show that the Hippo signaling pathway links determinants of cell polarity to polarization of the actin cytoskeleton in border cells. Upstream Hippo pathway components localize to contacts between border cells inside the cluster and signal through the Hippo and Warts kinases to polarize actin and promote border cell migration. Phosphorylation of the transcriptional coactivator Yorkie (Yki)/YAP by Warts does not mediate the function of this pathway in promoting border cell migration, but rather provides negative feedback to limit the speed of migration. Instead, Warts phosphorylates and inhibits the actin regulator Ena to activate F-actin Capping protein activity on inner membranes and thereby restricts F-actin polymerization mainly to the outer rim of the migrating cluster.
authors.affiliation: Epithelial Biology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3LY, England, UK.
authors.forename: Eliana P
authors.initials: EP
authors.lastname: Lucas
authors.forename: Ichha
authors.initials: I
authors.lastname: Khanal
authors.forename: Pedro
authors.initials: P
authors.lastname: Gaspar
authors.forename: Georgina C
authors.initials: GC
authors.lastname: Fletcher
authors.forename: Cedric
authors.initials: C
authors.lastname: Polesello
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tapon
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Thompson
mesh_terms: D051344:Actin Capping Proteins / Q000378:metabolism; D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D025461:Feedback, Physiological / Q000502:physiology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D019076:Transgenes / Q000502:physiology; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D051344:Actin Capping Proteins; D000199:Actins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C092744:ENA-VASP proteins; C503814:Yki protein, Drosophila; C093503:wts protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases