Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Robery, Steven UNSPECIFIED UNSPECIFIED UNSPECIFIED Tyson, Richard UNSPECIFIED UNSPECIFIED UNSPECIFIED Dinh, Christopher UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuspa, Adam UNSPECIFIED orcid.org/0000-0002-9156-149X UNSPECIFIED Noegel, Angelika A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bretschneider, Till UNSPECIFIED orcid.org/0000-0002-5317-603X UNSPECIFIED Andrews, Paul L. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Williams, Robin S. B. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language ENZYME-MEDIATED INTEGRATION; VALPROIC ACID; CELL MOTILITY; PHENYLTHIOCARBAMIDE; SENSITIVITY; NEURONS; GENE; CYTOKINESIS; PERCEPTION; DENATONIUM Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47150