Mutations in Bacchus reveal a tyramine-dependent nuclear regulator for acute ethanol sensitivity in Drosophila

作者：Chen Jiang; Wang Yonghua; Zhang Yan; Shen Ping^*

来源：Neuropharmacology, 2013, 67: 25-31.

DOI：10.1016/j.neuropharm.2012.10.013

• Bacchus
• CG9894
• Tyramine
• Octopamine
• Tyramine beta-hydroxylase
• Ethanol sensitivity
• Brain
• Drosophila

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 beta-hydroxylase (t beta h) activity that results in excessive conversion of tyramine (TA) to octopmaine (OA). Thus, t beta h 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.

• 出版日期2013-4