Drosophila A-kinase anchor protein 200, protein kinase A and diethylether anesthesia

摘要

To identify the cause of resistance to diethylether anesthesia mDrosophila A-kinase anchor protein 200 (DAKAP200) mutant, Eth~(AR)206, we tested genetic interaction with pka-RII~(EP2162). The double mutant analysis suggested the existence of genetic interaction between them. Anesthetic concentration of strains with altered endogenous protein kinase A (PKA) activity also showed altered sensitivity to diethylether. This suggests that DAKAP200 mutation altered ether sensitivity by affecting PKA signaling pathway. We speculate that DAKAP200 is involved in phosphorylation regulation of membrane proteins. Many ion channels are known to be directly regulated their conductivity by PKA phosphorylation in mammals and most homologs of those of Drosophila have conserved sequence for PKA phosphorylation site. These channels are considered to be main target molecules of anesthetics at the same time. Our proposal is that DAKAP200 protein affects sensitivity to anesthetics through phosphorylation regulation of ion channels.