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Chunk #29 — RESULTS — Survey for Ethanol Behavioral Mutants

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Ethanol-regulated genes that contribute to ethanol sensitivity and rapid tolerance in Drosophila.
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CG9238 encodes a protein phosphatase 1 (PP1) regulatory subunit, sharing 41% amino acid identity with mammalian protein targeting to glycogen (PTG). Mammalian PTG is an activator of PP1, promoting dephosphorylation of glycogen synthase and the production of glycogen as an energy store. Three independent transposon insertions in the CG9238 locus, 2 in the upstream regulatory region and one in the 5′-untranslated region of the gene, resulted in increased ΔDist with little apparent effect on Dist, sedation sensitivity, or sedation tolerance (Table 1 and Table S5). By microarray analysis CG9238 expression was transiently increased twofold, peaking 30 minutes after the termination of ethanol vapor exposure (Table S1). Transcript levels for CG9238 in the transposon insertion strain BG02516 were decreased to 53% ± 2% of controls. These data are consistent with CG9238 having an inhibitory effect on increased locomotor activity during ethanol exposure 2, suggesting that glycogen synthesis impacts ethanol tolerance in flies. Indeed, insulin signaling promotes glycogen synthesis in a PP1-dependent manner, and the insulin signaling pathway regulates ethanol sensitivity in flies (Brady and Saltiel, 2001; Corl et al., 2005).