title: Hrs regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila.
abstract: Signaling through tyrosine kinase receptors (TKRs) is thought to be modulated by receptor-mediated endocytosis and degradation of the receptor in the lysosome. However, factors that regulate endosomal sorting of TKRs are largely unknown. Here, we demonstrate that Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) is one such factor. Electron microscopy studies of hrs mutant larvae reveal an impairment in endosome membrane invagination and formation of multivesicular bodies (MVBs). hrs mutant animals fail to degrade active epidermal growth factor (EGF) and Torso TKRs, leading to enhanced signaling and altered embryonic patterning. These data suggest that Hrs and MVB formation function to downregulate TKR signaling.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lloyd
authors.forename: Richard
authors.initials: R
authors.lastname: Atkinson
authors.forename: Mark N
authors.initials: MN
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Pennetta
authors.forename: Hugo J
authors.initials: HJ
authors.lastname: Bellen
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D066246:ErbB Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007814:Larva / Q000502:physiology / Q000648:ultrastructure; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; C080148:tor protein, Drosophila