A novel human receptor involved in bitter tastant detection identified using Dictyostelium discoideum.
J Cell Sci
; 126(Pt 23): 5465-76, 2013 Dec 01.
Article
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| MEDLINE
| ID: mdl-24006265
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Feniltiourea
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Gusto
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Receptores de GABA-B
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Receptores Acoplados a Proteínas G
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Dictyostelium
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Fosfatidilinositol 3-Quinasa
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Año:
2013
Tipo del documento:
Article