title: Odorant-specific requirements for arrestin function in Drosophila olfaction.
abstract: The ability to modulate olfactory sensitivity is necessary to detect chemical gradients and discriminate among a multitude of odor stimuli. Desensitization of odorant receptors has been postulated to occur when arrestins prevent the activation of downstream second messengers. A paucity of in vivo data on olfactory desensitization prompts use of Drosophila melanogaster genetics to investigate arrestins' role in regulating olfactory signaling pathways. Physiological analysis of peripheral olfactory sensitivity reveals decreased responsiveness to a host of chemically distinct odorants in flies deficient for arrestin1 (arr1), arrestin2 (arr2), or both. These phenotypes are manifest in odorant- and dose- dependent fashions. Additionally, mutants display altered adaptive properties under a prolonged exposure paradigm. Behaviorally, arr1 mutants are impaired in olfactory-based orientation towards attractive odor sources. As the olfactory deficits vary according to chemical identity and concentration, they indicate that a spectrum of arrestin activity is essential for odor processing depending upon the particular olfactory pathway involved. Arrestin mutant phenotypes are hypothesized to be a consequence of down-regulation of olfactory signaling to avoid cellular excitotoxicity. Importantly, phenotypic rescue of olfactory defects in arr1(1) mutants is achieved through transgenic expression of wild-type arr1. Taken together, these data clearly indicate that arrestins are required in a stimulus-specific manner for wild type olfactory function and add another level of complexity to peripheral odor coding mechanisms that ultimately impact olfactory behavior.
authors.affiliation: Department of Biological Sciences, Vanderbilt University, 465 21st Avenue South, Nashville, Tennessee 37232, USA.
authors.forename: C Elaine
authors.initials: CE
authors.lastname: Merrill
authors.forename: Tracy M
authors.initials: TM
authors.lastname: Sherertz
authors.forename: William B
authors.initials: WB
authors.lastname: Walker
authors.forename: L J
authors.initials: LJ
authors.lastname: Zwiebel
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000096:Acetone / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D019390:Arrestins / Q000235:genetics / Q000378:metabolism*; D001522:Behavior, Animal; D000440:Butanols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004330:Drosophila; D029721:Drosophila Proteins; D004594:Electrophysiology / Q000379:methods; D007700:Kinetics; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D009154:Mutation; D009812:Odorants; D009833:Olfactory Pathways / Q000187:drug effects / Q000378:metabolism*; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D018035:Receptors, Odorant / Q000187:drug effects / Q000502:physiology; D012903:Smell / Q000187:drug effects / Q000502:physiology*; D013268:Stimulation, Chemical; D013997:Time Factors
chemical_list: D000085:Acetates; C504665:Arr1 protein, Drosophila; D019390:Arrestins; D000440:Butanols; D029721:Drosophila Proteins; D010750:Phosphoproteins; D018035:Receptors, Odorant; D000096:Acetone; C007650:ethyl acetate