Much of the information animals receive from the environment is gathered through G protein-coupled receptors (GPCRs). The ability to attenuate the signaling of these receptors would be most desirable in order to have an accurate perception of the environment. Additionally, the association between sensory inputs required for synaptic plasticity and learning should also be dependent on the precise timing and magnitude of signaling through these receptors. A primary function of arrestins, to down regulate activated GPCRs, suggests that these proteins are fundamental to the processes of sensory processing and association. The objective of the proposed research is to understand the function of the kurtz non-visual arrestin within the nervous system of Drosophila, and thereby determine the importance of agonist-induced desensitization of G protein-coupled receptors in behavior. The proposed studies will utilize mutants of the kurtz arrestin and newly generated transgenes to examine the function of the kurtz arrestin in sensory processing, and in both negatively-reinforced associative and operant conditioning learning paradigms. Specifically, the experiments will ask the question of whether the rapid desensitization and the resensitization of activated GPCRs is a requirement for accurate olfactory processing and in the processes of learning and memory. Additional experiments will characterize the biochemical and cellular properties of the kurtz arrestin. These results may allow for specific correlations to be drawn between behavioral phenotypes and the interactions with a specific GPCR. If agonist-induced desensitization of GPCRs is indeed critical to accurately time neuronal inputs so as to maximize informative associations, then arrestins may become attractive targets for cognitive enhancers that may eventually help treat aging associated memory decline as well as cognitive disorders including Alzheimer's disease.
| Johnson, Erik C; Tift, Frank W; McCauley, Anita et al. (2008) Functional characterization of kurtz, a Drosophila non-visual arrestin, reveals conservation of GPCR desensitization mechanisms. Insect Biochem Mol Biol 38:1016-22 |
| Benito, Juliana; Houl, Jerry H; Roman, Gregg W et al. (2008) The blue-light photoreceptor CRYPTOCHROME is expressed in a subset of circadian oscillator neurons in the Drosophila CNS. J Biol Rhythms 23:296-307 |
| Liu, Lingzhi; Davis, Ronald L; Roman, Gregg (2007) Exploratory activity in Drosophila requires the kurtz nonvisual arrestin. Genetics 175:1197-212 |
| Ge, Hong; Krishnan, Parthasarathy; Liu, Lingzhi et al. (2006) A Drosophila nonvisual arrestin is required for the maintenance of olfactory sensitivity. Chem Senses 31:49-62 |
| Ferris, Jacob; Ge, Hong; Liu, Lingzhi et al. (2006) G(o) signaling is required for Drosophila associative learning. Nat Neurosci 9:1036-40 |
