title: Delta and Egfr expression are regulated by Importin-7/Moleskin in Drosophila wing development.
abstract: Drosophila DIM-7 (encoded by the moleskin gene, msk) is the orthologue of vertebrate Importin-7. Both Importin-7 and Msk/DIM-7 function as nuclear import cofactors, and have been implicated in the control of multiple signal transduction pathways, including the direct nuclear import of the activated (phosphorylated) form of MAP kinase. We performed two genetic deficiency screens to identify deficiencies that similarly modified Msk overexpression phenotypes in both eyes and wings. We identified 11 total deficiencies, one of which removes the Delta locus. In this report, we show that Delta loss-of-function alleles dominantly suppress Msk gain-of-function phenotypes in the developing wing. We find that Msk overexpression increases both Delta protein expression and Delta transcription, though Msk expression alone is not sufficient to activate Delta protein function. We also find that Msk overexpression increases Egfr protein levels, and that msk gene function is required for proper Egfr expression in both developing wings and eyes. These results indicate a novel function for Msk in Egfr expression. We discuss the implications of these data with respect to the integration of Egfr and Delta/Notch signaling, specifically through the control of MAP kinase subcellular localization.
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Alysia D
authors.initials: AD
authors.lastname: Vrailas-Mortimer
authors.forename: Neena
authors.initials: N
authors.lastname: Majumdar
authors.forename: Ginnene
authors.initials: G
authors.lastname: Middleton
authors.forename: Evan M
authors.initials: EM
authors.lastname: Cooke
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Marenda
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005123:Eye / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D047908:Intracellular Signaling Peptides and Proteins; D028884:Karyopherins / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D018010:Receptors, Invertebrate Peptide / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D028884:Karyopherins; D008565:Membrane Proteins; D018010:Receptors, Invertebrate Peptide; C064045:delta protein; D011494:Protein Kinases; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors