Date of Graduation

2018

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Not Listed

Committee Chair

Eric E. Kelley

Committee Co-Chair

David P. Siderovski

Committee Member

Vincent Setola

Committee Member

William T. Stauber

Committee Member

Emidio E. Pistill

Abstract

The gustatory system subjects ingested food to ‘quality control’ that prevents consumption of harmful compounds while also regulating nutrient intake. A better understanding of the physiological regulation of taste will enhance our ability to facilitate the appropriate consumption of nutrients and improve overall health. Bitter, sweet, and umami tastes are detected by a family of G protein-coupled receptors (GPCRs) that associate with heterotrimeric G proteins and initiate intracellular signaling cascades after activation by tastant binding. ‘Regulators of G protein Signaling’ (RGS proteins) act as Ga-directed GTPase-accelerating proteins (GAPs) and thereby accelerate inactivation of GPCR-mediated signaling. Rgs21 is selectively expressed in tastantresponsive tissue, suggesting it likely facilitates the inactivation of the taste transduction pathway. We have assessed taste responses in Rgs21 knockout mice: bitterant, sweetener, and umami responses (metabotropic, Type II cell responses) are blunted in the absence of RGS21, whereas aversion to sour (ionotropic, Type III cell response) is unchanged. Notably, appetitive responses to NaCl are blunted in Rgs21-deficient mice as well, suggesting transduction of NaCl taste involves a GPCR and/or G protein signaling in Type II taste receptor cells. We suspect that RGS21 loss leads to hyperactivity of GPCRs in taste receptor cells, eventually causing prolonged desensitization and/or downregulation. Further work is needed to test this hypothesis and thus elucidate the mechanism(s) by which RGS21 affects peripheral taste signaling, including appetitive salt taste (a taste modality traditionally considered the exclusive domain of ionotropic signal transduction).

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