title: The LH/CG receptor activates canonical signaling pathway when expressed in Drosophila.
abstract: G-protein coupled receptors (GPCRs) and their ligands provide precise tissue regulation and are therefore often restricted to specific animal phyla. For example, the gonadotropins and their receptors are crucial for vertebrate reproduction but absent from invertebrates. In mammals, LHR mainly couples to the PKA signaling pathway, and CREB is the major transcription factor of this pathway. Here we present the results of expressing elements of the human gonadotropin system in Drosophila. Specifically, we generated transgenic Drosophila expressing the human LH/CG receptor (denoted as LHR), a constitutively active form of LHR, and an hCG analog. We demonstrate activation-dependent signaling by LHR to direct Drosophila phenotypes including lethality and specific midline defects; these phenotypes were due to LHR activation of PKA/CREB pathway activity. That the LHR can act in an invertebrate demonstrates the conservation of factors required for GPCR function among phylogenetically distant organisms. This novel gonadotropin model may assist the identification of new modulators of mammalian fertility by exploiting the powerful genetic and pharmacological tools available in Drosophila.
authors.affiliation: Dept. of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New-York, NY, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Graves
authors.affiliation: Dept. of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Markman
authors.affiliation: Dept. of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Alegranti
authors.affiliation: Dept. of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Jenia
authors.initials: J
authors.lastname: Gechtler
authors.affiliation: Dept. of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New-York, NY, USA.
authors.forename: Ruth I
authors.initials: RI
authors.lastname: Johnson
authors.affiliation: Dept. of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New-York, NY, USA.
authors.forename: Ross
authors.initials: R
authors.lastname: Cagan
authors.affiliation: Dept. of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. Electronic address: dbm@bgu.ac.il.
authors.forename: David
authors.initials: D
authors.lastname: Ben-Menahem
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004331:Drosophila melanogaster; D006801:Humans; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D011974:Receptors, LH
keywords: Gonadotropin evolution; LHR; Protein kinase A (PKA); cAMP response element-binding protein (CREB)