Taste perception is initiated by the interaction of sapid molecules with proteins on the surface of taste bud cells. These gustatory signals are subsequently transduced, processed in taste buds, coded and transmitted by cranial nerves to the brain. The long-term objective of our research program is to molecularly identify and functionally characterize key proteins that are involved in taste signal transduction and coding in taste buds, and decoding in the central nervous system, and eventually to reconstruct the molecular events of taste sensation and perception. We have used molecular cloning and functional analyses to identify and characterize a number of taste transduction components, including a G-protein coupled taste receptor T1R3, G protein subunits and a transient receptor potential ion channel TRPM5. In order to understand the molecular events downstream of TRPM5 and to reveal ion channels that are responsible for sour and salty tastes, we have determined the expression of six voltage-dependent calcium channels in taste bud cells.
The specific aims of this proposal are: 1) to identify and colocalize voltage-dependent calcium channel subunits with known taste signaling molecules in taste bud cells; 2) to heterologously express and functionally characterize novel isoforms of these voltage-dependent calcium channels isolated from taste buds; 3) to determine possible roles of these voltage-dependent calcium channels in taste bud synaptic transmission by monitoring the effect of pharmacological and genetic perturbation of these channels on the elevation of intracellular calcium concentrations and synaptic activity in taste bud cells in response to taste stimuli; 4) finally, to determine possible roles of these voltage-dependent calcium channels in taste sensation by gustatory nerve recording and animal behavioral tests with mutant animals. The results of these studies will yield new insights into the molecular mechanisms underling sour, salt, bitter, sweet and umami taste transduction, synaptic transmission and peripheral coding in the end organs of taste. The knowledge gained from this endeavor will further our understanding of the molecular bases of taste disorders such as malgeusia, dysgeusia, hypogeusia and ageusia and may lead to effective treatment. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC007487-02
Application #
7447335
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Davis, Barry
Project Start
2007-06-14
Project End
2012-05-31
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
2
Fiscal Year
2008
Total Cost
$288,298
Indirect Cost
Name
Monell Chemical Senses Center
Department
Type
DUNS #
088812565
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Feng, Pu; Chai, Jinghua; Zhou, Minliang et al. (2014) Interleukin-10 is produced by a specific subset of taste receptor cells and critical for maintaining structural integrity of mouse taste buds. J Neurosci 34:2689-701
Li, Feng; Zhou, Mingliang (2014) The interactions of TGF-beta signalling pathway and Jagged2/Notch1 pathway induce acanthosis in lingual epithelia. Pathology 46:555-65
Feng, Pu; Huang, Liquan; Wang, Hong (2014) Taste bud homeostasis in health, disease, and aging. Chem Senses 39:3-16
Li, Feng; Ponissery-Saidu, Samsudeen; Yee, Karen K et al. (2013) Heterotrimeric G protein subunit G?13 is critical to olfaction. J Neurosci 33:7975-84
Li, Feng; Zhou, Mingliang (2013) Conditional expression of the dominant-negative TGF-ýý receptor type II elicits lingual epithelial hyperplasia in transgenic mice. Dev Dyn 242:444-55
Xu, Jiang; Cao, Jie; Iguchi, Naoko et al. (2013) Functional characterization of bitter-taste receptors expressed in mammalian testis. Mol Hum Reprod 19:17-28
Feng, Pu; Zhao, Hang; Chai, Jinghua et al. (2012) Expression and secretion of TNF-ýý in mouse taste buds: a novel function of a specific subset of type II taste cells. PLoS One 7:e43140
Kim, Agnes; Feng, Pu; Ohkuri, Tadahiro et al. (2012) Defects in the peripheral taste structure and function in the MRL/lpr mouse model of autoimmune disease. PLoS One 7:e35588
Li, Feng; Zhou, Minliang (2012) Depletion of bitter taste transduction leads to massive spermatid loss in transgenic mice. Mol Hum Reprod 18:289-97
Iguchi, Naoko; Ohkuri, Tadahiro; Slack, Jay P et al. (2011) Sarco/Endoplasmic reticulum Ca2+-ATPases (SERCA) contribute to GPCR-mediated taste perception. PLoS One 6:e23165

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