The taste modality is critical not only to aid in the identification of food, but also to avoid consuming noxious chemicals. The long-term goal of the proposed research is to understand the molecular mechanisms underlying sweet and bitter taste transduction in the fruitfly, Drosophila melanogaster. The fruitfly has proven to be a valuable model organism for characterizing other sensory modalities, such as vision and olfaction;however, taste transduction has received less scrutiny. Recent studies indicate that the mammalian and Drosophila taste transduction pathways are initiated by G- protein coupled receptors. However, the mechanisms operating downstream of the Drosophila receptors are largely unknown. In mammals, there is evidence that taste transduction operates through a phospholipase C mediated signaling pathway that culminates with the activation of the TRPM5 channel. Nevertheless, many questions remain including the mechanisms of adaptation, the role of cAMP signaling in taste transduction, the mechanisms that regulate the gustatory channel in vivo and the proteins regulating the gustatory receptors. The goal,of the proposed research is to apply a combination of genetic, electrophysiological, cell and biochemical approaches in Drosophila to define the biochemical basis for taste transduction initiated by either attractive or aversive compounds.
The specific aims of this proposal are to test the hypotheses that: 1) the PI signaling proteins involved in Drosophila vision also function in taste, 2) cAMP signaling functions in Drosophila sweet and bitter transduction, 3) Gr66a is the caffeine receptor and misexpression of this receptor can elicit an attractive behavioral response to caffeine, and 4) the TRPA2 gustatory channel is regulated by calmodulin and interactions with the scaffold protein Homer. Given the apparent parallels between mammalian and Drosophila taste transduction, these studies should provide important new insights into the mechanisms of gustatory transduction that apply to human taste receptor cells.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC007864-05
Application #
7858398
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Davis, Barry
Project Start
2006-07-01
Project End
2011-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
5
Fiscal Year
2010
Total Cost
$297,589
Indirect Cost
Name
Johns Hopkins University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Xu, Chiwei; Luo, Junjie; He, Li et al. (2017) Oxidative stress induces stem cell proliferation via TRPA1/RyR-mediated Ca2+ signaling in the Drosophila midgut. Elife 6:
Luo, Junjie; Shen, Wei L; Montell, Craig (2017) TRPA1 mediates sensation of the rate of temperature change in Drosophila larvae. Nat Neurosci 20:34-41
Ni, Jinfei D; Baik, Lisa S; Holmes, Todd C et al. (2017) A rhodopsin in the brain functions in circadian photoentrainment in Drosophila. Nature 545:340-344
Huang, Jia; Liu, Weiwei; Qi, Yi-Xiang et al. (2016) Neuromodulation of Courtship Drive through Tyramine-Responsive Neurons in the Drosophila Brain. Curr Biol 26:2246-56
Zhang, Yali V; Aikin, Timothy J; Li, Zhengzheng et al. (2016) The Basis of Food Texture Sensation in Drosophila. Neuron 91:863-877
Shim, Jaewon; Lee, Youngseok; Jeong, Yong Taek et al. (2015) The full repertoire of Drosophila gustatory receptors for detecting an aversive compound. Nat Commun 6:8867
Liu, Chao; Montell, Craig (2015) Forcing open TRP channels: Mechanical gating as a unifying activation mechanism. Biochem Biophys Res Commun 460:22-5
Lee, Youngseok; Moon, Seok Jun; Wang, Yijin et al. (2015) A Drosophila Gustatory Receptor Required for Strychnine Sensation. Chem Senses 40:525-33
Liman, Emily R; Zhang, Yali V; Montell, Craig (2014) Peripheral coding of taste. Neuron 81:984-1000
Li, Zhengzheng; Ni, Jinfei D; Huang, Jia et al. (2014) Requirement for Drosophila SNMP1 for rapid activation and termination of pheromone-induced activity. PLoS Genet 10:e1004600

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