Robery, Steven, Tyson, Richard, Dinh, Christopher, Kuspa, Adam ORCID: 0000-0002-9156-149X, Noegel, Angelika A., Bretschneider, Till ORCID: 0000-0002-5317-603X, Andrews, Paul L. R. and Williams, Robin S. B. (2013). A novel human receptor involved in bitter tastant detection identified using Dictyostelium discoideum. J. Cell Sci., 126 (23). S. 5465 - 5477. CAMBRIDGE: COMPANY OF BIOLOGISTS LTD. ISSN 1477-9137

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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 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 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
Creators:
CreatorsEmailORCIDORCID Put Code
Robery, StevenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tyson, RichardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dinh, ChristopherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuspa, AdamUNSPECIFIEDorcid.org/0000-0002-9156-149XUNSPECIFIED
Noegel, Angelika A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bretschneider, TillUNSPECIFIEDorcid.org/0000-0002-5317-603XUNSPECIFIED
Andrews, Paul L. R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Williams, Robin S. B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-471503
DOI: 10.1242/jcs.136440
Journal or Publication Title: J. Cell Sci.
Volume: 126
Number: 23
Page Range: S. 5465 - 5477
Date: 2013
Publisher: COMPANY OF BIOLOGISTS LTD
Place of Publication: CAMBRIDGE
ISSN: 1477-9137
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ENZYME-MEDIATED INTEGRATION; VALPROIC ACID; CELL MOTILITY; PHENYLTHIOCARBAMIDE; SENSITIVITY; NEURONS; GENE; CYTOKINESIS; PERCEPTION; DENATONIUMMultiple languages
Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/47150

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