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A novel human receptor involved in bitter tastant detection identified using dictyostelium discoideum
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Robery, Steven, Tyson, Richard A. (Richard Anthony), Dinh, Christopher, Kuspa, Adam, Noegel, Angelika A., Bretschneider, Till, Andrews, P. L. R. (Paul L. R.) and Williams, Robin S. B. (2013) A novel human receptor involved in bitter tastant detection identified using dictyostelium discoideum. Journal of Cell Science, Volume 126 (Number 23). pp. 5465-5476. doi:10.1242/jcs.136440 ISSN 0021-9533.
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Official URL: http://dx.doi.org/10.1242/jcs.136440
Abstract
Detection of substances tasting bitter to humans occurs in diverse organisms including the social amoeba Dictyostelium discoideum. To establish a molecular mechanism for bitter tastant detection in Dictyostelium, we screened a mutant library for resistance to a commonly used bitter standard, phenylthiourea. This approach identified a G-protein-coupled receptor mutant, grlJ−, which showed a significantly increased tolerance to phenylthiourea in growth, survival and movement. This mutant was not resistant to a structurally dissimilar potent bitter tastant, denatonium benzoate, suggesting it is not a target for at least one other bitter tastant. Analysis of the cell-signalling pathway involved in the detection of phenylthiourea showed dependence upon heterotrimeric G protein and phosphatidylinositol 3-kinase activity, suggesting that this signalling pathway is responsible for the cellular effects of phenylthiourea. This is further supported by a phenylthiourea-dependent block in the transient cAMP-induced production of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in wild-type but not grlJ− cells. Finally, we have identified an uncharacterized human protein γ-aminobutyric acid (GABA) type B receptor subunit 1 isoform with weak homology to GrlJ that restored grlJ− sensitivity to phenylthiourea in cell movement and PIP3 regulation. Our results thus identify a novel pathway for the detection of the standard bitter tastant phenylthiourea in Dictyostelium and implicate a poorly characterized human protein in phenylthiourea-dependent cell responses.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | B Philosophy. Psychology. Religion > BF Psychology Q Science > QP Physiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre | ||||
| Library of Congress Subject Headings (LCSH): | Dictyostelium discoideum, Taste, Bitterness (Taste), Sensory receptors | ||||
| Journal or Publication Title: | Journal of Cell Science | ||||
| Publisher: | The Company of Biologists Ltd. | ||||
| ISSN: | 0021-9533 | ||||
| Official Date: | 2013 | ||||
| Dates: |
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| Volume: | Volume 126 | ||||
| Number: | Number 23 | ||||
| Page Range: | pp. 5465-5476 | ||||
| DOI: | 10.1242/jcs.136440 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | Universities Federation for Animal Welfare, Engineering and Physical Sciences Research Council (EPSRC) |
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