Molecular, physiological, and behavioral characterization of sensory arrestins in insect olfaction

Olfaction is the dominant sensory input in many organisms, particularly in driving host choice in insects that transmit disease. Activation of the olfactory system occurs when odorants stimulate G protein-coupled receptors (GPCRs); desensitization of GPCRs is largely carried out by the action of arrestins that uncouple receptors from the downstream signaling cascade. This report focuses on the role of arrestins in insect olfactory processing and seeks to test the hypothesis that arrestins play a crucial role in modulating odorant receptor sensitivity. Initially, these studies characterize the phylogenetic evolution, sequence features, and expression patterns of arrestins from the malaria vector mosquito Anopheles gambiae and the insect model system Drosophila melanogaster. Four arrestin genes have been identified from each species that appear to constitute four subclasses, presumably reflecting differences in function. While the insect arrestins were originally characterized from the Drosophila visual system, expression analysis reveals that insect arrestins are detected in a broader range of tissues. Subsequently, olfactory physiology and behavior is tested in Drosophila deficient for sensory arrestins in order to determine their contribution to olfactory function. The gross result of these investigations is that the loss of arrestins causes decreased olfactory sensitivity and decreased responsiveness to odor stimulation. Ultimately, these experiments yield novel insights into the role of desensitization in olfactory processing and may provide inventive strategies to disrupt olfaction in insect disease vectors and temper the spread of infectious worldwide health threats including malaria, dengue, and West Nile virus.