Most vertebrate species are responsive to five basic tastes: sweet, bitter, umami, sour and salty, each of which provides unique information on the nutritional content and safety of ingested food. Each of the five taste qualities is detected by a distinct subset of taste cells, which express distinct receptors and signaling molecules. While great progress has been made in understanding the molecules and pathways that mediate bitter, sweet, umami and salty tastes, relatively little is known about sour taste. The cells that detect sour taste have been shown to be defined by expression of the TRP ion channel PKD2L1, but the Pkd2l1 gene itself is dispensable for sour taste and the ionic mechanisms that underlie sensory responses to sour remain poorly understood. In recent work, using a mouse in which yellow fluorescent protein (YFP) was driven by the promoter of Pkd2l1, we showed that sour taste cells express a novel proton conductance which contributes to the response to acids. The specific goal of the current proposal is to identify the gene that encodes this proton conductance. To do this, we propose two specific aims.
In aim 1, we will use deep sequencing to perform transcription profiling of YFP-tagged sour cells and we will identify transcripts that ae enriched in Pkd2l1 cells and are likely to encode novel transmembrane proteins.
Under Aim 2, we will express the top candidates in a heterologous cell type and determine with patch clamp recording whether they generate a proton channel. The identification of this proton channel will represent an important step in understanding the taste system, and may help define a new class of ion channels. Taste is an essential way in which humans and other organisms regulate their ingestive behavior and the identification of key molecular components of taste signaling can therefore have a direct impact on human health and well-being.

Public Health Relevance

The proposed experiments use next generation sequencing of mRNA transcripts from genetically labeled taste cells to identify a novel ion channel that mediates sour taste transduction. Taste is an essential way in which humans and other organisms regulate their ingestive behavior and the identification of key molecular components of taste signaling can therefore have a direct impact on human health and well-being.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DC012747-02
Application #
8495312
Study Section
Special Emphasis Panel (ZRG1-IFCN-B (03))
Program Officer
Sullivan, Susan L
Project Start
2012-07-01
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2013
Total Cost
$276,802
Indirect Cost
$108,020
Name
University of Southern California
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Liman, Emily R (2014) TRPM5. Handb Exp Pharmacol 222:489-502
Liman, Emily R; Zhang, Yali V; Montell, Craig (2014) Peripheral coding of taste. Neuron 81:984-1000