title: Mutations in Bacchus reveal a tyramine-dependent nuclear regulator for acute ethanol sensitivity in Drosophila.
abstract: Fruit flies and humans display remarkably similar behavioral responses to ethanol intoxication. Here we report that loss-of-function mutations in the CG9894 gene (now named Bacchus or Bacc) attenuate ethanol sensitivity in flies. Bacc encodes a broadly expressed nuclear protein with a motif similar to ribosomal RNA-binding domains. The ethanol-related activity of Bacc was mapped to Tdc2-GAL4 neurons. Genetic and pharmacological analyses suggest that ethanol resistance of Bacc mutants is caused by increased tyramine β-hydroxylase (tβh) activity that results in excessive conversion of tyramine (TA) to octopmaine (OA). Thus, tβh and its negative regulator Bacc define a novel biogenic amine-mediated signaling pathway that regulates fly ethanol sensitivity. Importantly, elevated tbh activity has been shown to promote fighting behavior, raising the possibility that the Bacc/tbh pathway may regulate complex traits in addition to acute ethanol response.
authors.affiliation: Department of Cellular Biology and Biomedical and Health Sciences Institute, University of Georgia, 500 D. W. Brooks Drive, Athens, GA 30602, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Chen
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Shen
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001679:Biogenic Amines / Q000502:physiology; D002467:Cell Nucleus / Q000187:drug effects* / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004330:Drosophila; D029721:Drosophila Proteins / Q000187:drug effects / Q000235:genetics*; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D008969:Molecular Sequence Data; D009154:Mutation / Q000187:drug effects / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D014439:Tyramine / Q000502:physiology*
chemical_list: D001679:Biogenic Amines; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D000431:Ethanol; D014439:Tyramine