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Tonic activity of Galpha-gustducin regulates taste cell responsivity
Authors:Clapp Tod R  Trubey Kristina R  Vandenbeuch Aurelie  Stone Leslie M  Margolskee Robert F  Chaudhari Nirupa  Kinnamon Sue C
Affiliation:a Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States
b Rocky Mountain Taste and Smell Center, University of Colorado Denver, Aurora, CO 80045, United States
c Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, FL 33136, United States
d Program in Neurosciences, University of Miami Miller School of Medicine, Miami, FL 33136, United States
e Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, United States
Abstract:The taste-selective G protein, α-gustducin (α-gus) is homologous to α-transducin and activates phosphodiesterase (PDE) in vitro. α-Gus-knockout mice are compromized to bitter, sweet and umami taste stimuli, suggesting a central role in taste transduction. Here, we suggest a different role for Gα-gus. In taste buds of α-gus-knockout mice, basal (unstimulated) cAMP levels are high compared to those of wild-type mice. Further, H-89, a cAMP-dependent protein kinase inhibitor, dramatically unmasks responses to the bitter tastant denatonium in gus-lineage cells of knockout mice. We propose that an important role of α-gus is to maintain cAMP levels tonically low to ensure adequate Ca2+ signaling.
Keywords:CMF, calcium-magnesium free   CV, circumvallate   GFP, green fluorescent protein   GPCR, G protein-coupled receptor   Gus, gustducin   IP3R3, inositol trisphosphate receptor type III   PDE, phosphodiesterase   PKA, protein kinase A   PKC, protein kinase C   PLCβ2, phospholipase C β2
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