title: Dynein and Star interact in EGFR signaling and ligand trafficking.
abstract: Intracellular transport and processing of ligands is critical to the activation of signal transduction pathways that guide development. Star is an essential gene in Drosophila that has been implicated in the trafficking of ligands for epidermal growth factor (EGF) receptor signaling. The role of cytoplasmic motors in the endocytic and secretory pathways is well known, but the specific requirement of motors in EGF receptor transport has not been investigated. We identified Star in a screen designed to recover second-site modifiers of the dominant rough eye phenotype of the Glued mutation Gl(1). The Glued (Gl) locus encodes the p150 subunit of the dynactin complex, an activator of cytoplasmic dynein-driven motility. We show that alleles of Gl and dynein genetically interact with both Star and EGFR alleles. Similarly to mutations in Star, the Gl(1) mutation is capable of modifying the phenotypes of the EGFR mutation Ellipse. These genetic interactions suggest a model in which Star, dynactin and dynein cooperate in the trafficking of EGF ligands. In support of this model, overexpression of the cleaved, active Spitz ligand can partially bypass defective trafficking and suppress the genetic interactions. Our direct observations of live S2 cells show that export of Spitz-GFP from the endoplasmic reticulum, as well as the trafficking of Spitz-GFP vesicles, depends on both Star and dynein.
authors.affiliation: University of Minnesota, Department of Genetics, Cell Biology and Development, Minneapolis, MN 55455, USA.
authors.forename: Stanley J P
authors.initials: SJ
authors.lastname: Iyadurai
authors.forename: John T
authors.initials: JT
authors.lastname: Robinson
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Ma
authors.forename: Yungui
authors.initials: Y
authors.lastname: He
authors.forename: Sarah
authors.initials: S
authors.lastname: Mische
authors.forename: Min-Gang
authors.initials: MG
authors.lastname: Li
authors.forename: William
authors.initials: W
authors.lastname: Brown
authors.forename: Annabel
authors.initials: A
authors.lastname: Guichard
authors.forename: Ethan
authors.initials: E
authors.lastname: Bier
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Hays
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004398:Dyneins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic; D066246:ErbB Receptors / Q000378:metabolism* / Q000502:physiology; D005123:Eye / Q000033:anatomy & histology / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016254:Mutagenesis, Insertional / Q000502:physiology; D010641:Phenotype; D011485:Protein Binding; D021381:Protein Transport; D018626:Retroelements / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; D018626:Retroelements; C415248:S protein, Drosophila; D049452:Green Fluorescent Proteins; C076026:spi protein, Drosophila; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D004398:Dyneins