title: Targeted inactivation of the rickets receptor in muscle compromises Drosophila viability.
abstract: Bursicon is a hormone that modulates wing expansion, cuticle hardening and melanization in Drosophila melanogaster. Bursicon activity is mediated through its cognate G protein-coupled receptor (GPCR), rickets. We have developed a membrane-tethered bursicon construct that enables spatial modulation of rickets-mediated physiology in transgenic flies. Ubiquitous expression of tethered bursicon throughout development results in arrest at the pupal stage. The few organisms that eclose fail to undergo wing expansion. These phenotypes suggest that expression of tethered bursicon inhibits rickets-mediated function. Consistent with this hypothesis, we show in vitro that sustained stimulation of rickets by tethered bursicon leads to receptor desensitization. Furthermore, tissue-specific expression of the tethered bursicon inhibitor unraveled a critical role for rickets in a subset of adult muscles. Taken together, our findings highlight the utility of membrane-tethered inhibitors as important genetic/pharmacological tools to dissect the tissue-specific roles of GPCRs in vivo.
authors.affiliation: Tufts Medical Center, Molecular Cardiology Research Institute, Molecular Pharmacology Research Center, 800 Washington St, Box 7703, Boston, MA 02111, USA Program in Genetics, Sackler School of Graduate Biomedical Sciences, Tufts University, 145 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Benjamin N
authors.initials: BN
authors.lastname: Harwood
authors.affiliation: Tufts Medical Center, Molecular Cardiology Research Institute, Molecular Pharmacology Research Center, 800 Washington St, Box 7703, Boston, MA 02111, USA idraper@tuftsmedicalcenter.org akopin@tuftsmedicalcenter.org.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Draper
authors.affiliation: Tufts Medical Center, Molecular Cardiology Research Institute, Molecular Pharmacology Research Center, 800 Washington St, Box 7703, Boston, MA 02111, USA Program in Genetics, Sackler School of Graduate Biomedical Sciences, Tufts University, 145 Harrison Avenue, Boston, MA 02111, USA idraper@tuftsmedicalcenter.org akopin@tuftsmedicalcenter.org.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Kopin
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology*; D007301:Insect Hormones / Q000378:metabolism; D007447:Invertebrate Hormones / Q000378:metabolism* / Q000502:physiology*; D008675:Metamorphosis, Biological / Q000502:physiology*; D009132:Muscles / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D007301:Insect Hormones; D007447:Invertebrate Hormones; D043562:Receptors, G-Protein-Coupled; C002295:bursicon
keywords: Bursicon; Drosophila melanogaster; G protein-coupled receptor; Membrane-tethered ligand; Rickets