title: Identification of G protein-coupled receptors for Drosophila PRXamide peptides, CCAP, corazonin, and AKH supports a theory of ligand-receptor coevolution.
abstract: G-protein coupled receptors (GPCRs) are ancient, ubiquitous sensors vital to environmental and physiological signaling throughout organismal life. With the publication of the Drosophila genome, numerous "orphan" GPCRs have become available for functional analysis. Here we characterize two groups of GPCRs predicted as receptors for peptides with a C-terminal amino acid sequence motif consisting of -PRXamide (PRXa). Assuming ligand-receptor coevolution, two alternative hypotheses were constructed and tested. The insect PRXa peptides are evolutionarily related to the vertebrate peptide neuromedin U (NMU), or are related to arginine vasopressin (AVP), both of which have PRXa motifs. Seven Drosophila GPCRs related to receptors for NMU and AVP were cloned and expressed in Xenopus oocytes for functional analysis. Four Drosophila GPCRs in the NMU group (CG14575 [corrected], CG8795, CG9918, CG8784) are activated by insect PRXa pyrokinins, (-FXPRXamide), Cap2b-like peptides (-FPRXamide), or ecdysis triggering hormones (-PRXamide). Three Drosophila GPCRs in the vasopressin receptor group respond to crustacean cardioactive peptide (CCAP), corazonin, or adipokinetic hormone (AKH), none of which are PRXa peptides. These findings support a theory of coevolution for NMU and Drosophila PRXa peptides and their respective receptors.
authors.affiliation: Department of Entomology, 5429 Boyce Hall, University of California, Riverside, CA 92521, USA.
authors.forename: Yoonseong
authors.initials: Y
authors.lastname: Park
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Kim
authors.forename: Michael E
authors.initials: ME
authors.lastname: Adams
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002116:Calcitonin / Q000235:genetics / Q000502:physiology*; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins; D019204:GTP-Binding Proteins / Q000502:physiology*; D007301:Insect Hormones / Q000235:genetics / Q000502:physiology*; D019476:Insect Proteins; D008024:Ligands; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology*; D009842:Oligopeptides / Q000235:genetics / Q000502:physiology*; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D013379:Substrate Specificity
chemical_list: C489221:Crz protein, Drosophila; D029721:Drosophila Proteins; D007301:Insect Hormones; D019476:Insect Proteins; D008024:Ligands; D009479:Neuropeptides; D009842:Oligopeptides; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C044833:adipokinetic hormone; C060602:corazonin protein, insect; C037553:katacalcin; D002116:Calcitonin; D019204:GTP-Binding Proteins; D011761:Pyrrolidonecarboxylic Acid