Journal article
Regulator of G-protein Signaling-21 (RGS21) Is an Inhibitor of Bitter Gustatory Signaling Found in Lingual and Airway Epithelia
The Journal of biological chemistry, Vol.287(50), pp.41706-41719
12/07/2012
DOI: 10.1074/jbc.M112.423806
PMCID: PMC3516720
PMID: 23095746
Abstract
The gustatory system detects tastants and transmits signals to the brain regarding ingested substances and nutrients. Although tastant receptors and taste signaling pathways have been identified, little is known about their regulation. Because bitter, sweet, and umami taste receptors are G protein-coupled receptors (GPCRs), we hypothesized that regulators of G protein signaling (RGS) proteins may be involved. The recent cloning of RGS21 from taste bud cells has implicated this protein in the regulation of taste signaling; however, the exact role of RGS21 has not been precisely defined. Here, we sought to determine the role of RGS21 in tastant responsiveness. Biochemical analyses confirmed in silico predictions that RGS21 acts as a GTPase-accelerating protein (GAP) for multiple G protein α subunits, including adenylyl cyclase-inhibitory (Gαi) subunits and those thought to be involved in tastant signal transduction. Using a combination of in situ hybridization, RT-PCR, immunohistochemistry, and immunofluorescence, we demonstrate that RGS21 is not only endogenously expressed in mouse taste buds but also in lung airway epithelial cells, which have previously been shown to express components of the taste signaling cascade. Furthermore, as shown by reverse transcription-PCR, the immortalized human airway cell line 16HBE was found to express transcripts for tastant receptors, RGS21, and downstream taste signaling components. Over- and underexpression of RGS21 in 16HBE cells confirmed that RGS21 acts to oppose bitter tastant signaling to cAMP and calcium second messenger changes. Our data collectively suggests that RGS21 modulates bitter taste signal transduction.
Background: RGS21 is expressed in tastant-responsive lingual epithelium, but with unknown function.
Results: RGS21 accelerated intrinsic GTPase activity of multiple Gα subunits; RGS21 over- and underexpression in epithelial cells modulated bitterant responsiveness.
Conclusion: RGS21 is a negative regulator of bitterant signal transduction.
Significance: RGS21 represents a nonreceptor regulatory component of gustatory signaling that alters sensitivity of bitterant responsiveness in an endogenous, cellular context.
Details
- Title: Subtitle
- Regulator of G-protein Signaling-21 (RGS21) Is an Inhibitor of Bitter Gustatory Signaling Found in Lingual and Airway Epithelia
- Creators
- Staci P Cohen - University of North Carolina at Chapel HillBrian K Buckley - University of North Carolina at Chapel HillMickey Kosloff - University of HaifaAlaina L Garland - University of North Carolina at Chapel HillDustin E Bosch - University of North Carolina at Chapel HillGang Cheng - University of North Carolina at Chapel HillHarish Radhakrishna - Coca Cola (United States)Michael D Brown - Coca Cola (United States)Francis S Willard - University of North Carolina at Chapel HillVadim Y Arshavsky - Duke UniversityRobert Tarran - University of North Carolina at Chapel HillDavid P Siderovski - University of North Carolina at Chapel HillAdam J Kimple - University of North Carolina at Chapel Hill
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.287(50), pp.41706-41719
- DOI
- 10.1074/jbc.M112.423806
- PMID
- 23095746
- PMCID
- PMC3516720
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 12/07/2012
- Academic Unit
- Pathology
- Record Identifier
- 9984200021602771
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