TY - JOUR
T1 - Development of full sweet, umami, and bitter taste responsiveness requires Regulator of G protein Signaling-21 (RGS21)
AU - Schroer, Adam B.
AU - Gross, Joshua D.
AU - Kaski, Shane W.
AU - Wix, Kim
AU - Siderovski, David P.
AU - Vandenbeuch, Aurelie
AU - Setola, Vincent
N1 - Funding Information:
This work was supported, in part, by the West Virginia University E.J. Van Liere Medicine Professorship and William W. Fleming Pharmacology Trust endowments [to D.P.S. and A.S., respectively]. Trpm5 in situ hybridization data were generated by the Baylor College of Medicine’s RNA In Situ Hybridization Core supported by NIH grant S10 OD016167.
Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press. All rights reserved.
PY - 2018/5/23
Y1 - 2018/5/23
N2 - The mammalian tastes of sweet, umami, and bitter are initiated by activation of G protein-coupled receptors (GPCRs) of the T1R and T2R families on taste receptor cells. GPCRs signal via nucleotide exchange and hydrolysis, the latter hastened by GTPase-accelerating proteins (GAPs) that include the Regulators of G protein Signaling (RGS) protein family. We previously reported that RGS21, uniquely expressed in Type II taste receptor cells, decreases the potency of bitter-stimulated T2R signaling in cultured cells, consistent with its in vitro GAP activity. However, the role of RGS21 in organismal responses to GPCR-mediated tastants was not established. Here, we characterized mice lacking the Rgs21 fifth exon. Eliminating Rgs21 expression had no effect on body mass accumulation (a measure of alimentation), fungiform papillae number and morphology, circumvallate papillae morphology, and taste bud number. Two-bottle preference tests, however, revealed that Rgs21-null mice have blunted aversion to quinine and denatonium, and blunted preference for monosodium glutamate, the sweeteners sucrose and SC45647, and (surprisingly) NaCl. Observed reductions in GPCR-mediated tastant responses upon Rgs21 loss are opposite to original expectations, given that loss of RGS21-a GPCR signaling negative regulator-should lead to increased responsiveness to tastant-mediated GPCR signaling (all else being equal). Yet, reduced organismal tastant responses are consistent with observations of reduced chorda tympani nerve recordings in Rgs21-null mice. Reduced tastant-mediated responses and behaviors exhibited by adult mice lacking Rgs21 expression since birth have thus revealed an underappreciated requirement for a GPCR GAP to establish the full character of tastant signaling.
AB - The mammalian tastes of sweet, umami, and bitter are initiated by activation of G protein-coupled receptors (GPCRs) of the T1R and T2R families on taste receptor cells. GPCRs signal via nucleotide exchange and hydrolysis, the latter hastened by GTPase-accelerating proteins (GAPs) that include the Regulators of G protein Signaling (RGS) protein family. We previously reported that RGS21, uniquely expressed in Type II taste receptor cells, decreases the potency of bitter-stimulated T2R signaling in cultured cells, consistent with its in vitro GAP activity. However, the role of RGS21 in organismal responses to GPCR-mediated tastants was not established. Here, we characterized mice lacking the Rgs21 fifth exon. Eliminating Rgs21 expression had no effect on body mass accumulation (a measure of alimentation), fungiform papillae number and morphology, circumvallate papillae morphology, and taste bud number. Two-bottle preference tests, however, revealed that Rgs21-null mice have blunted aversion to quinine and denatonium, and blunted preference for monosodium glutamate, the sweeteners sucrose and SC45647, and (surprisingly) NaCl. Observed reductions in GPCR-mediated tastant responses upon Rgs21 loss are opposite to original expectations, given that loss of RGS21-a GPCR signaling negative regulator-should lead to increased responsiveness to tastant-mediated GPCR signaling (all else being equal). Yet, reduced organismal tastant responses are consistent with observations of reduced chorda tympani nerve recordings in Rgs21-null mice. Reduced tastant-mediated responses and behaviors exhibited by adult mice lacking Rgs21 expression since birth have thus revealed an underappreciated requirement for a GPCR GAP to establish the full character of tastant signaling.
KW - Gustatory
KW - Mouse
KW - Regulator of G protein signaling-21 (RGS21)
KW - Taste buds
KW - Taste perception
UR - http://www.scopus.com/inward/record.url?scp=85047661591&partnerID=8YFLogxK
U2 - 10.1093/chemse/bjy024
DO - 10.1093/chemse/bjy024
M3 - Article
C2 - 29701767
AN - SCOPUS:85047661591
SN - 0379-864X
VL - 43
SP - 367
EP - 378
JO - Chemical Senses
JF - Chemical Senses
IS - 5
ER -