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Media type:
E-Article
Title:
A novel human receptor involved in bitter tastant detection identified using the model organism Dictyostelium discoideum
Contributor:
Robery, Steven;
Tyson, Richard;
Dinh, Christopher;
Kuspa, Adam;
Noegel, Angelika A.;
Bretschneider, Till;
Andrews, Paul L. R.;
Williams, Robin S. B.
Description:
<jats:p>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−, showing 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 this signalling pathway is responsible for phenylthiourea cellular effects. This is further supported by a phenylthiourea-dependent block in the transient cAMP-induced production of PIP3 in wild type but not grlJ− cells. Finally, we have identified an uncharacterized human protein gamma-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 data thus identifies a novel pathway for the detection of the standard bitter tastant, phenylthiourea, in Dictyostelium and implicates a poorly characterized human protein in phenylthiourea dependent cell responses.</jats:p>