Tonic activity of Gα-gustducin regulates taste cell responsivity

Clapp, Tod R.; Trubey, Kristina R.; Vandenbeuch, Aurelie; Stone, Leslie M.; Margolskee, Robert F.; Chaudhari, Nirupa; Kinnamon, Sue C.

doi:10.1016/j.febslet.2008.10.007

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Volume 582, Issue 27 , Pages 3783-3787, 12 November 2008

Tonic activity of Gα-gustducin regulates taste cell responsivity

Edited by Jesus Avila

Tod R. Clapp
- Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States
- Rocky Mountain Taste and Smell Center, University of Colorado Denver, Aurora, CO 80045, United States
Kristina R. Trubey
- Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, FL 33136, United States
Aurelie Vandenbeuch
- Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States
- Rocky Mountain Taste and Smell Center, University of Colorado Denver, Aurora, CO 80045, United States
Leslie M. Stone
- Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States
- Rocky Mountain Taste and Smell Center, University of Colorado Denver, Aurora, CO 80045, United States
Robert F. Margolskee
- Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, United States
Nirupa Chaudhari
- Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, FL 33136, United States
- Program in Neurosciences, University of Miami Miller School of Medicine, Miami, FL 33136, United States
- These authors contributed equally to the work.
Sue C. Kinnamon
- Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States
- Rocky Mountain Taste and Smell Center, University of Colorado Denver, Aurora, CO 80045, United States
- Corresponding author. Address: Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States. Fax: +1 970 491 7907.
- These authors contributed equally to the work.

Received 28 August 2008; received in revised form 3 October 2008; accepted 6 October 2008. published online 17 October 2008.

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.

Abbreviations: 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