Functions of human bitter taste receptors depend on N‐glycosylation

Reichling, Claudia; Meyerhof, Wolfgang; Behrens, Maik

doi:10.1111/j.1471-4159.2008.05453.x

Cited by 60 publications

(55 citation statements)

References 46 publications

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“…S4A) with similar sites predicted in both Q8NHA5 and GABA B-1B (supplementary material Fig. S4B,C), where they have been associated with bitter taste receptor function in previous studies (Bufe et al, 2002;Reichling et al, 2008). Because our data support a role for the overactivation of Q8NHA5 in response to phenylthiourea, we conclude that this receptor could be activated by phenylthiourea, with the potential of regulating neuropsychiatric function.…”

Section: Discussionsupporting

confidence: 81%

A novel human receptor involved in bitter tastant detection identified using the model organism Dictyostelium discoideum

Robery

Tyson

Dinh

et al. 2013

Journal of Cell Science

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SummaryDetection 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 2 , 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 (PIP 3 ) in wild-type but not grlJ 2 cells. Finally, we have identified an uncharacterized human protein c-aminobutyric acid (GABA) type B receptor subunit 1 isoform with weak homology to GrlJ that restored grlJ 2 sensitivity to phenylthiourea in cell movement and PIP 3 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.

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Section: Discussionsupporting

confidence: 81%

A novel human receptor involved in bitter tastant detection identified using the model organism Dictyostelium discoideum

Robery

Tyson

Dinh

et al. 2013

Journal of Cell Science

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“…The ATrM1 clone was not functional probably because of missing 4 Asn-linked putative glycosylation sites. It has been shown that glycosylation is critical for GPCR function [8, 34, 44, 45]. In marked contrast, HEK293/Gα16gust44 cells expressing ATrM2 or ATrM3 receptors were both robustly activated by AT in a dose-responsive manner.…”

Section: Discussionmentioning

confidence: 99%

Functional characterization of an allatotropin receptor expressed in the corpora allata of mosquitoes

et al. 2012

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Allatotropin is an insect neuropeptide with pleiotropic actions on a variety of different tissues. In the present work we describe the identification, cloning and functional and molecular characterization of an Aedes aegypti allatotropin receptor (AeATr) and provide a detailed quantitative study of the expression of the AeATr gene in the adult mosquito. Analysis of the tissue distribution of AeATr mRNA in adult female revealed high transcript levels in the nervous system (brain, abdominal, thoracic and ventral ganglia), corpora allata-corpora cardiaca complex and ovary. The receptor is also expressed in heart, hindgut and male testis and accessory glands. Separation of the corpora allata (CA) and corpora cardiaca followed by analysis of gene expression in the isolated glands revealed expression of the AeATr primarily in the CA. In the female CA, the AeATr mRNA levels were low in the early pupae, started increasing 6 hours before adult eclosion and reached a maximum 24 hours after female emergence. Blood feeding resulted in a decrease in transcript levels. The pattern of changes of AeATr mRNA resembles the changes in JH biosynthesis. Fluorometric Imaging Plate Reader recordings of calcium transients in HEK293 cells expressing the AeATr showed a selective response to A. aegypti allatotropin stimulation in the low nanomolar concentration range. Our studies suggest that the AeATr play a role in the regulation of JH synthesis in mosquitoes.

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“…However, all the T2Rs share a conserved consensus site for asparagine-linked glycosylation within the second extracellular loop. This site is known to be important for membrane targeting and receptor function (Reichling et al, 2008). T2Rs enable humans to perceive thousands of bitter compounds, since most receptors are able to recognize several different types of ligands or even whole chemical families.…”

Section: Accepted Manuscriptmentioning

confidence: 99%