title: The Caenorhabditis elegans seven-transmembrane protein ODR-10 functions as an odorant receptor in mammalian cells.
abstract: The nematode Caenorhabditis elegans exhibits behavioral responses to many volatile odorants. Chemotaxis toward one such odorant, diacetyl (butanedione), requires the function of a seven-transmembrane receptor protein encoded by the odr-10 gene. To determine directly whether ODR-10 protein is an odorant receptor, it is necessary to express the protein in a heterologous system and show that it responds to diacetyl by activation of a G protein signaling pathway. Here we demonstrate that human cells expressing ODR-10 on their surfaces exhibit a transient elevation in intracellular Ca2+ levels after diacetyl application. Volatile compounds that differ from diacetyl only by the addition of a methyl group (2,3-pentanedione) or the absence of a keto group (butanone) are not ODR-10 agonists. Behavioral responses to these compounds are not dependent on odr-10 function, so ODR-10 specificity in human cells resembles in vivo specificity. The apparent affinity of ODR-10 for diacetyl observed in human cells is consistent with the diacetyl concentration ranges that allow efficient nematode chemotaxis. ODR-10 expressed in human cells also responds to two anionic compounds, pyruvate and citrate, which are metabolic precursors used for diacetyl production by certain bacterial species. Ca2+ elevation in response to ODR-10 activation is due to release from intracellular stores.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: J H
authors.initials: JH
authors.lastname: Chou
authors.forename: J
authors.initials: J
authors.lastname: Bradley
authors.forename: C I
authors.initials: CI
authors.lastname: Bargmann
authors.forename: K
authors.initials: K
authors.lastname: Zinn
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002633:Chemotaxis; D019343:Citric Acid / Q000494:pharmacology; D003931:Diacetyl / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011487:Protein Conformation; D019289:Pyruvic Acid / Q000494:pharmacology; D018035:Receptors, Odorant / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; C109039:ODR-10 protein, C elegans; D018035:Receptors, Odorant; D011994:Recombinant Proteins; D019343:Citric Acid; D019289:Pyruvic Acid; D019204:GTP-Binding Proteins; D003931:Diacetyl; D002118:Calcium