The research goals of the Section of Molecular Neuroscience are to define the molecular mechanisms underlying the development and function of mammalian chemosensory systems. Research efforts this past year have been directed towards 1) establishing functional assays for bitter taste receptors, 2) determining the DNA regulatory sequences required to direct taste cell gene expression, and 3) identifying novel genes selectively expressed in taste cells. 1) To better understand the specificities and signal transduction pathways of the G-protein coupled bitter receptors, we have cloned and constructed expression vectors with the 23 identified human bitter receptors. Preliminary expression studies indicate that expression of at least one of the bitter receptors conferred the ability of a heterologous cell to respond to bitter compounds. Panels of bitter-tasting compounds will be used in both cell-based and in vitro reconstitution assays to determine additional ligand/receptor pairs and to characterize the specificities and coupling properties of bitter receptors. 2) Previously, we identified T1R3, a mammalian sweet receptor, and demonstrated that it was specifically expressed in a subset of taste cells. To define the DNA regulatory sequences responsible for directing the taste cell expression of T1R3, we have determined the genomic structure of the T1R3 gene and engineered a series of constructs with varying extents of the T1R3 upstream region driving the expression of green fluorescent protein. Transgenic mice carrying these constructs have been derived and are currently being analyzed. 3) In an attempt to identify novel genes involved in taste perception, we generated a normalized, subtracted cDNA library from taste tissue. Sequence analyses of 10000 clones from this library indicate that it is highly enriched in taste receptor cell specific genes. In situ hybridization expression studies with selected clones have led to the identification of several genes specifically expressed in taste cells. Two of these genes encode putative components of the taste cell signal transduction pathway including a novel ion channel and a novel G-protein coupled receptor.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Intramural Research (Z01)
Project #
1Z01DC000034-06
Application #
6674019
Study Section
(LMB)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2002
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