title: Localization of Hippo signalling complexes and Warts activation in vivo.
abstract: Hippo signalling controls organ growth and cell fate by regulating the activity of the kinase Warts. Multiple Hippo pathway components localize to apical junctions in epithelial cells, but the spatial and functional relationships among components have not been clarified, nor is it known where Warts activation occurs. We report here that Hippo pathway components in Drosophila wing imaginal discs are organized into distinct junctional complexes, including separate distributions for Salvador, Expanded, Warts and Hippo. These complexes are reorganized on Hippo pathway activation, when Warts shifts from associating with its inhibitor Jub to its activator Expanded, and Hippo concentrates at Salvador sites. We identify mechanisms promoting Warts relocalization, and using a phospho-specific antisera and genetic manipulations, identify where Warts activation occurs: at apical junctions where Expanded, Salvador, Hippo and Warts overlap. Our observations define spatial relationships among Hippo signalling components and establish the functional importance of their localization to Warts activation.
authors.affiliation: Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: Shuguo
authors.initials: S
authors.lastname: Sun
authors.affiliation: Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: B V V G
authors.initials: BV
authors.lastname: Reddy
authors.affiliation: Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Irvine
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction; D014921:Wings, Animal / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D000099317:Hippo Kinases
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C465504:sav protein, Drosophila; C093503:wts protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases