title: Regulator of G-protein signaling-21 (RGS21) is an inhibitor of bitter gustatory signaling found in lingual and airway epithelia.
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 (Gα(i)) 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.
authors.affiliation: Department of Pharmacology, University of North Carolina Neuroscience Center, University of North Carolina, Chapel Hill, North Carolina 27599-7365, USA.
authors.forename: Staci P
authors.initials: SP
authors.lastname: Cohen
authors.forename: Brian K
authors.initials: BK
authors.lastname: Buckley
authors.forename: Mickey
authors.initials: M
authors.lastname: Kosloff
authors.forename: Alaina L
authors.initials: AL
authors.lastname: Garland
authors.forename: Dustin E
authors.initials: DE
authors.lastname: Bosch
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
authors.forename: Harish
authors.initials: H
authors.lastname: Radhakrishna
authors.forename: Michael D
authors.initials: MD
authors.lastname: Brown
authors.forename: Francis S
authors.initials: FS
authors.lastname: Willard
authors.forename: Vadim Y
authors.initials: VY
authors.lastname: Arshavsky
authors.forename: Robert
authors.initials: R
authors.lastname: Tarran
authors.forename: David P
authors.initials: DP
authors.lastname: Siderovski
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Kimple
mesh_terms: D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002522:Chlorocebus aethiops; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism*; D020555:GTP-Binding Protein Regulators / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D020710:RGS Proteins; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013649:Taste / Q000502:physiology*; D013650:Taste Buds / Q000166:cytology / Q000378:metabolism*
chemical_list: D020555:GTP-Binding Protein Regulators; D020710:RGS Proteins; C512065:RGS21 protein, human; D000242:Cyclic AMP; D002118:Calcium