Mapping the Foci of Arrestin's Role in Ethanol Sedation

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DESCRIPTION (provided by applicant): The objective of this proposal is to develop a genetic framework for the processes controlling alcohol sedation. The framework will be produced through epistasis analysis on several defined signaling mutants in Drosophila. This framework will center on the Drosophila non-visual arrestin kurtz, and will define genetic interactions that modulate behavioral sensitivity to alcohol. Mutants in kurtz are hypersensitive to the sedative effects alcohol. This sensitivity is rescued by the targeted expression of a kurtz cDNA within the nervous system, demonstrating a neural requirement for arrestin activity in the normal resistance to alcohol's intoxicating properties. The proposed experiments will examine whether this requirement is a developmental function of kurtz, or whether the absence of arrestin activity leaves the nervous system physiologically sensitized to the sedative effects of alcohol. The experiments will also map the neural foci for the function of kurtz in regulating alcohol sedation through gain-of-function rescue experiments. With this deeper understanding of where and when kurtz functions to modulate alcohol sensitivity, we will define additional molecules that interact with kurtz in the development of alcohol intoxication. One such interaction, in which the krz1 mutation can repress the alcohol sensitivity phenotype of the rutabaga typeI adenylyl cylase, has already been demonstrated. The data gained from these expriements will provide a functional dissection of the molecular processes that modify an animal's sensitivity to alcohol.