Functions of Opsins in Drosophila Taste Leung, Nicole Y.; Thakur, Dhananjay P.; Gurav, Adishthi S. ...
CB/Current biology,
04/2020, Letnik:
30, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Rhodopsin is a light receptor comprised of an opsin protein and a light-sensitive retinal chromophore. Despite more than a century of scrutiny, there is no evidence that opsins function in ...chemosensation. Here, we demonstrate that three Drosophila opsins, Rh1, Rh4, and Rh7, are needed in gustatory receptor neurons to sense a plant-derived bitter compound, aristolochic acid (ARI). The gustatory requirements for these opsins are light-independent and do not require retinal. The opsins enabled flies to detect lower concentrations of aristolochic acid by initiating an amplification cascade that includes a G-protein, phospholipase Cβ, and the TRP channel, TRPA1. In contrast, responses to higher levels of the bitter compound were mediated through direct activation of TRPA1. Our study reveals roles for opsins in chemosensation and raise questions concerning the original roles for these classical G-protein-coupled receptors.
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•Opsins are needed for bitter taste in Drosophila•Opsins are directly activated by bitter tastants•Role for opsins in taste is independent of light and retinal•Opsins sense low levels of tastants via a signaling cascade that includes TRPA1
Rhodopsins sense light and consist of an opsin and retinal. Using flies, Leung et al. find that opsins detect bitter compounds and are needed for taste. The opsins promote sensing low amounts of chemicals via a signaling cascade that includes TRPA1. This function is independent of light and retinal and reveals a role for opsins as chemosensors.
Web search tools are widely used by the general public to obtain health-related information, and analysis of search data is often suggested for public health monitoring. We analyzed popularity of ...searches related to smell loss and taste loss, recently listed as symptoms of COVID-19. Searches on sight loss and hearing loss, which are not considered as COVID-19 symptoms, were used as control. Google Trends results per region in Italy or state in the US were compared to COVID-19 incidence in the corresponding geographical areas. The COVID-19 incidence did not correlate with searches for non-symptoms, but in some weeks had high correlation with taste and smell loss searches, which also correlated with each other. Correlation of the sensory symptoms with new COVID-19 cases for each country as a whole was high at some time points, but decreased (Italy) or dramatically fluctuated over time (US). Smell loss searches correlated with the incidence of media reports in the US. Our results show that popularity of symptom searches is not reliable for pandemic monitoring. Awareness of this limitation is important during the COVID-19 pandemic, which continues to spread and to exhibit new clinical manifestations, and for potential future health threats.
Bitter taste receptors (TAS2Rs) mediate aversive response to toxic food, which is often bitter. These G‐protein‐coupled receptors are also expressed in extraoral tissues, and emerge as novel targets ...for therapeutic indications such as asthma and infection. Our goal was to identify ligands of the broadly tuned TAS2R14 among clinical drugs. Molecular properties of known human bitter taste receptor TAS2R14 agonists were incorporated into pharmacophore‐ and shape‐based models and used to computationally predict additional ligands. Predictions were tested by calcium imaging of TAS2R14‐transfected HEK293 cells. In vitro testing of the virtual screening predictions resulted in 30–80% success rates, and 15 clinical drugs were found to activate the TAS2R14. hERG potassium channel, which is predominantly expressed in the heart, emerged as a common off‐target of bitter drugs. Despite immense chemical diversity of known TAS2R14 ligands, novel ligands and previously unknown polypharmacology of drugs were unraveled by in vitro screening of computational predictions. This enables rational repurposing of traditional and standard drugs for bitter taste signaling modulation for therapeutic indications.—Levit, A., Nowak, S., Peters, M., Wiener, A., Meyerhof, W., Behrens, M., Niv, M. Y. The bitter pill: clinical drugs that activate the human bitter taste receptor TAS2R14. FASEB J. 28, 1181–1197 (2014). www.fasebj.org
We have previously shown that l-glucose, the non-caloric enantiomer of d-glucose, activates the human sweet taste receptor T1R2/T1R3 transiently expressed in HEK293T cells. Here, we show that d- and ...l-glucose can also activate T1R2 and T1R3 expressed without the counterpart monomer. Serine mutation to alanine in residue 147 in the binding site of T1R3 VFT domain, completely abolishes T1R3S147A activation by either l- or d-glucose, while T1R2/T1R3S147A responds in the same way as T1R2 expressed without its counterpart. We further show that the original T1R2 reference sequence (NM_152232.1) is less sensitive by almost an order of magnitude than the reference sequence at the time this study was performed (NM_152232.4). We find that out of the four differing positions, it is the R317G in the VFT domain of T1R2, that is responsible for this effect in vitro. It is significant for both practical assay sensitivity and because glycine is found in this position in ~20% of the world population. While the effects of the mutations and the partial transfections were similar for d and l enantiomers, their dose-response curves remained distinct, with l-glucose reaching an early plateau.
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Bitter taste is innately aversive and thought to protect against consuming poisons. Bitter taste receptors (Tas2Rs) are G-protein coupled receptors, expressed both orally and ...extra-orally and proposed as novel targets for several indications, including asthma. Many clinical drugs elicit bitter taste, suggesting the possibility of drugs re-purposing. On the other hand, the bitter taste of medicine presents a major compliance problem for pediatric drugs. Thus, efficient tools for predicting, measuring and masking bitterness of active pharmaceutical ingredients (APIs) are required by the pharmaceutical industry. Here we highlight the BitterDB database of bitter compounds and survey the main computational approaches to prediction of bitter taste based on compound's chemical structure. Current in silico bitterness prediction methods provide encouraging results, can be constantly improved using growing experimental data, and present a reliable and efficient addition to the APIs development toolbox.
Bitter mouth-rinse affects emotions Dubovski, Nitzan; Ert, Eyal; Niv, Masha Y.
Food quality and preference,
09/2017, Letnik:
60
Journal Article
Recenzirano
•Mouth rinse with bitter solutions lowered PANAS mood scores.•The negative effect on mood depended on perceiving the solution as bitter.•Mood scores were not affected by mouth rinse with sucrose ...solution.•Tested risk-taking and trust measures were not affected by neither bitter nor sweet taste.
The sense of taste enables evaluation of food and is an important regulator of food consumption. In general, sweet is an attractive taste modality that leads to ingestion of nutritive food, while sour and bitter are aversive taste modalities that lead to avoidance of spoiled and toxic food. Recent studies suggest inter-connections between taste, emotion and cognition. Here we test the potential effects of two prototypical taste modalities, bitter and sweet, on emotions and on generalized avoidance behaviors, such as risk aversion and mistrust.
Three experiments included over 250 participants who tasted, without swallowing, one of the following stimuli: water control, quinine solution, sucrose solution, quinine-sucrose mixture solution, or propylthiouracil (PROP) solution. The participants had to identify the taste, rank its intensity, perform seemingly unrelated behavioral tasks, and fill a PANAS mood questionnaire.
Our results indicate that oral exposure to bitter compounds negatively correlates with mood scores; that the effect depends on perceiving the solution as bitter; that bitter mouth rinse can lower PANAS mood score and that there is a potential asymmetry in the effects of bitter and sweet taste modalities on mood.
Obesity is a global epidemic that causes morbidity and impaired quality of life. The melanocortin receptor 4 (MC4R) is at the crux of appetite, energy homeostasis, and body-weight control in the ...central nervous system and is a prime target for anti-obesity drugs. Here, we present the cryo-electron microscopy (cryo-EM) structure of the human MC4R-G
signaling complex bound to the agonist setmelanotide, a cyclic peptide recently approved for the treatment of obesity. The work reveals the mechanism of MC4R activation, highlighting a molecular switch that initiates satiation signaling. In addition, our findings indicate that calcium (Ca
) is required for agonist, but not antagonist, efficacy. These results fill a gap in the understanding of MC4R activation and could guide the design of future weight-management drugs.
•Trehalose and sucrose can mask bitterness at certain KCl concentrations, without masking saltiness.•Perceived sweetness of sugar varies among subjects and is reduced by KCl.•Chemical effects alone ...cannot account for KCl taste modulation by sugars.
Dramatic increase in NaCl consumption lead to sodium intake beyond health guidelines. KCl substitution helps reduce sodium intake but results in a bitter-metallic off-taste. Two disaccharides, trehalose and sucrose, were tested in order to untangle the chemical (increase in effective concentration of KCl due to sugar addition) from the sensory effects. The bitter-metallic taste of KCl was reduced by these sugars, while saltiness was enhanced or unaltered. The perceived sweetness of sugar, regardless of its type and concentration, was an important factor in KCl taste modulation. Though KCl was previously shown to increase the chemical activity of trehalose but not of sucrose, we found that it suppressed the perceived sweetness of both sugars. Therefore, sensory integration was the dominant factor in the tested KCl-sugar combinations.
This study aimed at identifying whether the bitter-tasting amino acids l-arginine (l-ARG) and l-isoleucine (l-ILE) differentially regulate mechanisms of gastric acid secretion in human parietal cells ...(HGT-1 cells) via activation of bitter taste sensing receptors (T2Rs). In a first set of experiments, involvement of T2Rs in l-ARG and l-ILE-modulated proton secretion was demonstrated by co-treatment of HGT-1 cells with T2R antagonists. Subsequent whole genome screenings by means of cDNA arrays revealed T2R1 as a prominent target for both amino acids. Next, the functional role of T2R1 was verified by means of a T2R1 CRISPR-Cas9 knock-out approach. Here, the effect of l-ARG on proton secretion decreased by 65.7 ± 21.9% and the effect of l-ILE increased by 93.2 ± 24.1% in HGT-1 T2R1 ko versus HGT-1 wt cells (p < 0.05). Overall, our results indicate differential effects of l-ARG and l-ILE on proton secretion in HGT-1 cells and our molecular docking studies predict distinct binding for these amino acids in the binding site of T2R1. Further studies will elucidate whether the mechanism of differential effects involves structure-specific ligand-biased signaling of T2R1 or additional cellular targets.
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