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The stability of tastant detection by mouse lingual chemosensory tissue requires Regulator of G protein Signaling-21 (RGS21)

Authors
  • Schroer, Adam B1
  • Branyan, Kayla W2
  • Gross, Joshua D3
  • Chantler, Paul D2
  • Kimple, Adam J4
  • Vandenbeuch, Aurelie5
  • Siderovski, David P6
  • 1 Department of Neuroscience, West Virginia University School of Medicine, 64 Medical Center Drive, Morgantown, WV 26506 , (United States)
  • 2 Division of Exercise Physiology, West Virginia University School of Medicine, 64 Medical Center Drive, Morgantown, WV 26506 , (United States)
  • 3 Department of Cell Biology, Duke University Medical Center, 307 Research Drive, Durham, NC 27710 , (United States)
  • 4 Department of Otolaryngology and Marsico Lung Institute, UNC School of Medicine, , 170 Manning Drive, Chapel Hill, NC 27599-7070 , (United States)
  • 5 Department of Otolaryngology, University of Colorado–Denver, Anschutz Medical Campus, 12700 E. 19th Avenue, Aurora, CO 80045 , (United States)
  • 6 Department of Pharmacology & Neuroscience, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107 , (United States)
Type
Published Article
Journal
Chemical Senses
Publisher
Oxford University Press
Publication Date
Oct 29, 2021
Volume
46
Identifiers
DOI: 10.1093/chemse/bjab048
PMID: 34718440
PMCID: PMC8785950
Source
PubMed Central
Keywords
Disciplines
  • AcademicSubjects/SCI01180
License
Unknown

Abstract

The T1R and T2R families of G protein-coupled receptors (GPCRs) initiate tastant perception by signaling via guanine nucleotide exchange and hydrolysis performed by associated heterotrimeric G proteins (Gαβγ). Heterotrimeric G protein signal termination is sped up by Gα-directed GTPase-accelerating proteins (GAPs) known as the Regulators of G protein Signaling (RGS proteins). Of this family, RGS21 is highly expressed in lingual epithelial cells and we have shown it acting in vitro to decrease the potency of bitterants on cultured cells. However, constitutive RGS21 loss in mice reduces organismal response to GPCR-mediated tastants—opposite to expectations arising from observed in vitro activity of RGS21 as a GAP and inhibitor of T2R signaling. Here, we show reduced quinine aversion and reduced sucrose preference by mice lacking RGS21 does not result from post-ingestive effects, as taste-salient brief-access tests confirm the reduced bitterant aversion and reduced sweetener preference seen using two-bottle choice testing. Eliminating Rgs21 expression after chemosensory system development, via tamoxifen-induced Cre recombination in eight week-old mice, led to a reduction in quinine aversive behavior that advanced over time, suggesting that RGS21 functions as a negative regulator to sustain stable bitter tastant reception. Consistent with this notion, we observed downregulation of multiple T2R proteins in the lingual tissue of Rgs21 -deficient mice. Reduced tastant-mediated responses exhibited by mice lacking Rgs21 expression either since birth or in adulthood has highlighted the potential requirement for a GPCR GAP to maintain the full character of tastant signaling, likely at the level of mitigating receptor downregulation.

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