Modulating the function of G protein coupled receptors (GPCRs) is a common means by which the sensitivity of signaling pathways can be increased or decreased as circumstances dictate. Different accessory enhancing proteins can affect GPCR responsiveness in several ways: regulate expression, target subcellular localization, promote proper folding, or enhance association with G proteins. Olfactory receptors, rhodopsin and taste receptors are amongst the sensory GPCRs for which one or more accessory enhancing proteins have been found to modulate the receptor's response function - particularly important for receptors that must function to detect sensory stimuli over several orders of magnitude. Meyerhof and colleagues and we have found multiple RTPs (Receptor Transporting Proteins) and REEPs (Receptor Expression Enhancing Proteins) to be present in taste tissue. Contrary to the results of Meyerhof's group we observed that REEP2 is selectively expressed in taste cells and enhances the function of both sweet and bitter taste receptors. The experiments proposed here functionally characterize the roles of RTPs and REEPs, particularly REEP2, in promoting taste receptor function. In this proposal we combine molecular, cellular, transgenic, physiological and behavioral methods to determine: 1. which receptor enhancing proteins are expressed in which taste cells;2. which receptor enhancing proteins interact with which taste receptors and by which sites;3. how REEP2 and other REEPs/RTPs enhance sweet receptor function;4. if REEP2 and and/or other REEPs/RTPs are involved in taste receptor function in vivo. This multidisciplinary approach has promise for providing significant new insights into the function and regulation of bitter, sweet and amino acid taste receptors within taste cells. This proposal has medical relevance to gustatory function, appetite, satiety, diabetes and obesity.

Public Health Relevance

In many sensory systems accessory proteins regulate or enhance the function of the sensory receptor. We have found that one such receptor enhancing protein, REEP2, is selectively expressed in taste cells and enhances responses from bitter and sweet taste receptors but not from non-gustatory receptors. The experiments proposed to determine how REEP2 and other REEPs and RTPs interact with taste receptors and if this occurs in vivo have medical relevance to gustatory function, appetite, satiety, diabetes and obesity.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC003155-14
Application #
8460931
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
1998-08-01
Project End
2015-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
14
Fiscal Year
2013
Total Cost
$295,126
Indirect Cost
$99,711
Name
Monell Chemical Senses Center
Department
Type
DUNS #
088812565
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Lee, Robert J; Kofonow, Jennifer M; Rosen, Philip L et al. (2014) Bitter and sweet taste receptors regulate human upper respiratory innate immunity. J Clin Invest 124:1393-405
Kokrashvili, Zaza; Yee, Karen K; Ilegems, Erwin et al. (2014) Endocrine taste cells. Br J Nutr 111 Suppl 1:S23-9
Mosinger, Bedrich; Redding, Kevin M; Parker, M Rockwell et al. (2013) Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility. Proc Natl Acad Sci U S A 110:12319-24
Zukerman, Steven; Glendinning, John I; Margolskee, Robert F et al. (2013) Impact of T1r3 and Trpm5 on carbohydrate preference and acceptance in C57BL/6 mice. Chem Senses 38:421-37
Nosrat, Irina V; Margolskee, Robert F; Nosrat, Christopher A (2012) Targeted taste cell-specific overexpression of brain-derived neurotrophic factor in adult taste buds elevates phosphorylated TrkB protein levels in taste cells, increases taste bud size, and promotes gustatory innervation. J Biol Chem 287:16791-800
Eddy, Meghan C; Eschle, Benjamin K; Peterson, Darlene et al. (2012) A conditioned aversion study of sucrose and SC45647 taste in TRPM5 knockout mice. Chem Senses 37:391-401
Jiang, Peihua; Josue, Jesusa; Li, Xia et al. (2012) Major taste loss in carnivorous mammals. Proc Natl Acad Sci U S A 109:4956-61
Yasumatsu, Keiko; Ogiwara, Yoko; Takai, Shingo et al. (2012) Umami taste in mice uses multiple receptors and transduction pathways. J Physiol 590:1155-70
Yoshida, Ryusuke; Ohkuri, Tadahiro; Jyotaki, Masafumi et al. (2010) Endocannabinoids selectively enhance sweet taste. Proc Natl Acad Sci U S A 107:935-9
Murata, Yoshihiro; Yasuo, Toshiaki; Yoshida, Ryusuke et al. (2010) Action potential-enhanced ATP release from taste cells through hemichannels. J Neurophysiol 104:896-901

Showing the most recent 10 out of 51 publications