title: The palmitoyltransferase Approximated promotes growth via the Hippo pathway by palmitoylation of Fat.
abstract: The large protocadherin Fat functions to promote Hippo pathway activity in restricting tissue growth. Loss of Fat leads to accumulation of the atypical myosin Dachs at the apical junctional region, which in turn promotes growth by inhibiting Warts. We previously identified Approximated (App), a DHHC domain palmitoyltransferase, as a negative regulator of Fat signaling in growth control. We show here that App promotes growth by palmitoylating the intracellular domain of Fat, and that palmitoylation negatively regulates Fat function. Independently, App also recruits Dachs to the apical junctional region through protein-protein association, thereby stimulating Dachs's activity in promoting growth. Further, we show that palmitoylation by App functions antagonistically to phosphorylation by Discs-overgrown, which activates Fat. Together, these findings suggest a model in which App promotes Dachs activity by simultaneously repressing Fat via posttranslational modification and recruiting Dachs to the apical junctional region, thereby promoting tissue growth.
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637.|Department of Zoology, University of Wisconsin, Madison, WI 53706.
authors.forename: Hitoshi
authors.identifier: http://orcid.org/0000-0002-5401-6433
authors.initials: H
authors.lastname: Matakatsu
authors.affiliation: Department of Zoology, University of Wisconsin, Madison, WI 53706.
authors.forename: Seth S
authors.identifier: http://orcid.org/0000-0002-5857-4408
authors.initials: SS
authors.lastname: Blair
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637 rfehon@uchicago.edu.
authors.forename: Richard G
authors.identifier: http://orcid.org/0000-0003-4889-2602
authors.initials: RG
authors.lastname: Fehon
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D048149:Casein Kinase 1 epsilon / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D005838:Genotype; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D054878:Lipoylation; D009218:Myosins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D011485:Protein Binding; D000072417:Protein Domains; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000099317:Hippo Kinases
chemical_list: D000217:Acyltransferases; D048149:Casein Kinase 1 epsilon; D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009218:Myosins; D017346:Protein Serine-Threonine Kinases; C492999:dachs protein, Drosophila; C113519:dco protein, Drosophila; C472307:ft protein, Drosophila; C000619644:App protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases