title: The novel gene tank, a tumor suppressor homolog, regulates ethanol sensitivity in Drosophila.
abstract: In both mammalian and insect models of ethanol intoxication, high doses of ethanol induce motor impairment and eventually sedation. Sensitivity to the sedative effects of ethanol is inversely correlated with risk for alcoholism. However, the genes regulating ethanol sensitivity are largely unknown. Based on a previous genetic screen in Drosophila for ethanol sedation mutants, we identified a novel gene, tank (CG15626), the homolog of the mammalian tumor suppressor EI24/PIG8, which has a strong role in regulating ethanol sedation sensitivity. Genetic and behavioral analyses revealed that tank acts in the adult nervous system to promote ethanol sensitivity. We localized the function of tank in regulating ethanol sensitivity to neurons within the pars intercerebralis that have not been implicated previously in ethanol responses. We show that acutely manipulating the activity of all tank-expressing neurons, or of pars intercerebralis neurons in particular, alters ethanol sensitivity in a sexually dimorphic manner, since neuronal activation enhanced ethanol sedation in males, but not females. Finally, we provide anatomical evidence that tank-expressing neurons form likely synaptic connections with neurons expressing the neural sex determination factor fruitless (fru), which have been implicated recently in the regulation of ethanol sensitivity. We suggest that a functional interaction with fru neurons, many of which are sexually dimorphic, may account for the sex-specific effect induced by activating tank neurons. Overall, we have characterized a novel gene and corresponding set of neurons that regulate ethanol sensitivity in Drosophila.
authors: Department of Anatomy and Program in Neuroscience, University of California, San Francisco, California 94158, USA. ad3030@columbia.edu
authors: Anita V
authors: AV
authors: Devineni
authors: Mark
authors: M
authors: Eddison
authors: Ulrike
authors: U
authors: Heberlein
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001522:Behavior, Animal / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007473:Ion Channels; D008967:Molecular Biology; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D034622:RNA Interference / Q000502:physiology; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002492:Central Nervous System Depressants; D029721:Drosophila Proteins; C526185:EI24 protein, mouse; D007473:Ion Channels; D009687:Nuclear Proteins; C582682:TANK protein, Drosophila; C484406:TANK protein, human; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C475684:TrpA1 protein, Drosophila; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins; D000431:Ethanol
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