PMID- 34718440 OWN - NLM STAT- MEDLINE DCOM- 20220117 LR - 20220531 IS - 1464-3553 (Electronic) IS - 0379-864X (Print) IS - 0379-864X (Linking) VI - 46 DP - 2021 Jan 1 TI - The stability of tastant detection by mouse lingual chemosensory tissue requires Regulator of G protein Signaling-21 (RGS21). LID - 10.1093/chemse/bjab048 [doi] LID - bjab048 AB - 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 (Galphabetagamma). Heterotrimeric G protein signal termination is sped up by Galpha-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. CI - (c) The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Schroer, Adam B AU - Schroer AB AD - Department of Neuroscience, West Virginia University School of Medicine, 64 Medical Center Drive, Morgantown, WV 26506, USA. FAU - Branyan, Kayla W AU - Branyan KW AD - Division of Exercise Physiology, West Virginia University School of Medicine, 64 Medical Center Drive, Morgantown, WV 26506, USA. FAU - Gross, Joshua D AU - Gross JD AD - Department of Cell Biology, Duke University Medical Center, 307 Research Drive, Durham, NC 27710, USA. FAU - Chantler, Paul D AU - Chantler PD AD - Division of Exercise Physiology, West Virginia University School of Medicine, 64 Medical Center Drive, Morgantown, WV 26506, USA. FAU - Kimple, Adam J AU - Kimple AJ AD - Department of Otolaryngology and Marsico Lung Institute, UNC School of Medicine , 170 Manning Drive, Chapel Hill, NC 27599-7070, USA. FAU - Vandenbeuch, Aurelie AU - Vandenbeuch A AD - Department of Otolaryngology, University of Colorado-Denver, Anschutz Medical Campus, 12700 E. 19th Avenue, Aurora, CO 80045, USA. FAU - Siderovski, David P AU - Siderovski DP AUID- ORCID: 0000-0002-0688-8210 AD - Department of Pharmacology & Neuroscience, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA. LA - eng GR - R01 DA048153/DA/NIDA NIH HHS/United States GR - E.J. Van Liere and William W. Fleming Pharmacology Trust endowments/ PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - England TA - Chem Senses JT - Chemical senses JID - 8217190 RN - 0 (RGS Proteins) RN - 0 (Receptors, G-Protein-Coupled) RN - EC 3.6.1.- (GTP-Binding Proteins) SB - IM MH - Animals MH - GTP-Binding Proteins MH - Mice MH - *RGS Proteins/genetics/metabolism MH - Receptors, G-Protein-Coupled/genetics/metabolism MH - Signal Transduction MH - Taste PMC - PMC8785950 OTO - NOTNLM OT - bitter gustation OT - mouse OT - regulator of G protein signaling-21 (RGS21) OT - salt gustation OT - sweet gustation OT - taste perception EDAT- 2021/11/01 06:00 MHDA- 2022/01/18 06:00 PMCR- 2021/10/29 CRDT- 2021/10/31 20:59 PHST- 2021/11/01 06:00 [pubmed] PHST- 2022/01/18 06:00 [medline] PHST- 2021/10/31 20:59 [entrez] PHST- 2021/10/29 00:00 [pmc-release] AID - 6414340 [pii] AID - bjab048 [pii] AID - 10.1093/chemse/bjab048 [doi] PST - ppublish SO - Chem Senses. 2021 Jan 1;46:bjab048. doi: 10.1093/chemse/bjab048.