This report describes characterization of the fly response to alcohol using Drosophila genes within the P13K/AKT signaling pathway. Neural perturbations of expression of fly genes Pi3K92E (orthologous to human PIK3C kinase catalytic subunit genes), Pdk1 (ortholog of human PDPK1 kinase), Akt1 (orthologous to human AKT kinase genes), and Pten (ortholog of human PTEN phosphatase) all produce changes in ethanol sensitivity.
In a genetic screen for mutants exhibiting altered sensitivity to the sedating effect of ethanol, an insertion allele of the fly gene aru exhibited hypersensitivity (see FBhh0000688). Since the human orthologs of aru, EPS8 and related genes, have been implicated in signaling via the PI3K/AKT pathway, additional Drosophila genes within these pathways were assessed for ethanol sensitivity in adult flies. Using a pan-neuronal driver, various overexpression, dominant gain-of-function, and RNAi-effected loss-of-function perturbations were tested.
[updated Jan. 2018 by FlyBase; FBrf0222196]