The research goals of the Section of Molecular Neuroscience are to define the molecular mechanisms underlying the development and function of mammalian chemosensory systems. During the past year, studies aimed at identifying molecules important for gustatory system function were initiated. By examining genome sequences generated by the Human Genome Project, we identified a candidate taste receptor gene, designated T1R3, predicted to encode a novel family 3 G-protein coupled receptor. Based on human sequences, the corresponding mouse T1R3 gene was also cloned and shown to be selectively expressed by taste receptor cells on the tongue. The mouse T1R3 gene was mapped using radiation hybrid mapping to the distal end of chromosome 4 within the genetically defined interval for the Sac locus, a major genetic determinant of sweet preference in mice. Consistent with its candidacy as the Sac locus gene, we demonstrated that the T1R3 genes from taster (Sac +) and non-tasters (Sac -) strains of mice displayed several polymorphisms (resulting in 6 amino acid substitutions). These results, together with expression data, suggest T1R3 may be a sweet receptor and, if so, would be the first mammalian sweet receptor identified. Functional studies to further characterize T1R3 are underway. In an attempt to identify novel genes involved in taste perception, we generated a normalized, subtracted cDNA library from taste tissue. Sequence analysis of 5000 clones from this library indicate that it is highly enriched in taste receptor cell specific genes. In situ hybridization expression studies with several clones has led to the identification of three gene specifically expressed in taste receptor cells. The roles of these gene in taste receptor cell function are being characterized.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Intramural Research (Z01)
Project #
1Z01DC000034-05
Application #
6513786
Study Section
(LMB)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Deafness & Other Communication Disorders
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Bartel, Dianna L; Sullivan, Susan L; Lavoie, Elise G et al. (2006) Nucleoside triphosphate diphosphohydrolase-2 is the ecto-ATPase of type I cells in taste buds. J Comp Neurol 497:1-12
LopezJimenez, Nelson D; Cavenagh, Margaret M; Sainz, Eduardo et al. (2006) Two members of the TRPP family of ion channels, Pkd1l3 and Pkd2l1, are co-expressed in a subset of taste receptor cells. J Neurochem 98:68-77
LopezJimenez, Nelson D; Sainz, Eduardo; Cavenagh, Margaret M et al. (2005) Two novel genes, Gpr113, which encodes a family 2 G-protein-coupled receptor, and Trcg1, are selectively expressed in taste receptor cells. Genomics 85:472-82
Sullivan, Susan L (2002) Mammalian chemosensory receptors. Neuroreport 13:A9-17
Sainz, E; Korley, J N; Battey, J F et al. (2001) Identification of a novel member of the T1R family of putative taste receptors. J Neurochem 77:896-903
Li, H; Wu, D K; Sullivan, S L (1999) Characterization and expression of sema4g, a novel member of the semaphorin gene family. Mech Dev 87:169-73