• Molecules and Cells
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• v.40 no.5
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• pp.331-338
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• 2017

Regulation of feeding is essential for animal survival. The pharyngeal sense organs can act as a second checkpoint of food quality, due to their position between external taste organs such as the labellum which initially assess food quality, and the digestive tract. Growing evidence provides support that the pharyngeal sensory neurons regulate feeding, but much is still unknown. We found that a pair of gustatory receptor neurons in the LSO, a Drosophila adult pharyngeal organ which expresses four gustatory receptors, is involved in feeding inhibition in response to high concentrations of sodium ions. RNAi experiments and mutant analysis showed that the gustatory receptor Gr2a is necessary for this process. This feeding preference determined by whether a food source is perceived as appetizing or not is influenced by nutritional conditions, such that when the animal is hungry, the need for energy dominates over how appealing the food source is. Our results provide experimental evidence that factors involved in feeding function in a context-dependent manner.

• Molecules and Cells
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• v.46 no.7
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• pp.451-460
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• 2023

Animals generally prefer nutrients and avoid toxic and harmful chemicals. Recent behavioral and physiological studies have identified that sweet-sensing gustatory receptor neurons (GRNs) in Drosophila melanogaster mediate appetitive behaviors toward fatty acids. Sweet-sensing GRN activation requires the function of the ionotropic receptors IR25a, IR56d, and IR76b, as well as the gustatory receptor GR64e. However, we reveal that hexanoic acid (HA) is toxic rather than nutritious to D. melanogaster. HA is one of the major components of the fruit Morinda citrifolia (noni). Thus, we analyzed the gustatory responses to one of major noni fatty acids, HA, via electrophysiology and proboscis extension response (PER) assay. Electrophysiological tests show this is reminiscent of arginine-mediated neuronal responses. Here, we determined that a low concentration of HA induced attraction, which was mediated by sweet-sensing GRNs, and a high concentration of HA induced aversion, which was mediated by bitter-sensing GRNs. We also demonstrated that a low concentration of HA elicits attraction mainly mediated by GR64d and IR56d expressed by sweet-sensing GRNs, but a high concentration of HA activates three gustatory receptors (GR32a, GR33a, and GR66a) expressed by bitter-sensing GRNs. The mechanism of sensing HA is biphasic in a dose dependent manner. Furthermore, HA inhibit sugar-mediated activation like other bitter compounds. Taken together, we discovered a binary HA-sensing mechanism that may be evolutionarily meaningful in the foraging niche of insects.

• Molecules and Cells
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• v.43 no.6
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• pp.530-538
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• 2020

The Gustatory system enables animals to detect toxic bitter chemicals, which is critical for insects to survive food induced toxicity. Cucurbitacin is widely present in plants such as cucumber and gourds that acts as an anti-herbivore chemical and an insecticide. Cucurbitacin has a harmful effect on insect larvae as well. Although various beneficial effects of cucurbitacin such as alleviating hyperglycemia have also been documented, it is not clear what kinds of molecular sensors are required to detect cucurbitacin in nature. Cucurbitacin B, a major bitter component of bitter melon, was applied to induce action potentials from sensilla of a mouth part of the fly, labellum. Here we identify that only Gr33a is required for activating bitter-sensing gustatory receptor neurons by cucurbitacin B among available 26 Grs, 23 Irs, 11 Trp mutants, and 26 Gr-RNAi lines. We further investigated the difference between control and Gr33a mutant by analyzing binary food choice assay. We also measured toxic effect of Cucurbitacin B over 0.01 mM range. Our findings uncover the molecular sensor of cucurbitacin B in Drosophila melanogaster. We propose that the discarded shell of Cucurbitaceae can be developed to make a new insecticide.

• Molecules and Cells
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• v.40 no.10
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• pp.731-736
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• 2017

Taste sensitivity to sugars plays an essential role in the initiation of feeding behavior. In Drosophila melanogaster, recent studies have identified several gustatory receptor (Gr) genes required for sensing sweet compounds. However, it is as yet undetermined how these GRs function as taste receptors tuned to a wide range of sugars. Among sugars, fructose has been suggested to be detected by a distinct receptor from other sugars. While GR43A has been reported to sense fructose in the brain, it is not expressed in labellar gustatory receptor neurons that show taste response to fructose. In contrast, the Gr64a-Gr64f gene cluster was recently shown to be associated with fructose sensitivity. Here we sought to decipher the genes required for fructose response among Gr64a-Gr64f genes. Unexpectedly, the qPCR analyses for these genes show that labellar expression levels of Gr64d and Gr64e are higher in fructose low-sensitivity flies than in high-sensitivity flies. Moreover, gustatory nerve responses to fructose in labellar sensilla are higher in Gr64d and Gr64f mutant lines than in mutant flies of the other Gr64a-Gr64f genes. These data suggest the possibility that deletion of GR64D or GR64F may indirectly induce enhanced fructose sensitivity in the labellum. Finally, we conclude that response to fructose cannot be explained by a single one of the Gr64a-Gr64f genes.

• Molecules and Cells
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• v.39 no.4
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• pp.310-315
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• 2016

Coumarin is a phenolic compound that mainly affects the liver due to its metabolization into a toxic compound. The deterrent and ovicidal activities of coumarin in insect models such as Drosophila melanogaster have been reported. Here we explore the molecular mechanisms by which these insects protect themselves and their eggs from this toxic plant metabolite. Coumarin was fatal to the flies in a dosage-dependent manner. However, coumarin feeding could be inhibited through activation of the aversive gustatory receptor neurons (GRNs), but not the olfactory receptor neurons. Furthermore, three gustatory receptors, GR33a, GR66a, and GR93a, functioned together in coumarin detection by the proboscis. However, GR33a, but not GR66a and GR93a, was required to avoid coumarin during oviposition, with a choice of the same substrates provided as in binary food choice assay. Taken together, these findings suggest that anti-feeding activity and oviposition to avoid coumarin occur via separate mechanisms.

• Molecules and Cells
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• v.44 no.12
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• pp.900-910
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• 2021

Sour is one of the fundamental taste modalities that enable taste perception in animals. Chemoreceptors embedded in taste organs are pivotal to discriminate between different chemicals to ensure survival. Animals generally prefer slightly acidic food and avoid highly acidic alternatives. We recently proposed that all acids are aversive at high concentrations, a response that is mediated by low pH as well as specific anions in Drosophila melanogaster. Particularly, some carboxylic acids such as glycolic acid, citric acid, and lactic acid are highly attractive to Drosophila compared with acetic acid. The present study determined that attractive carboxylic acids were mediated by broadly expressed Ir25a and Ir76b, as demonstrated by a candidate mutant library screen. The mutant deficits were completely recovered via wild-type cDNA expression in sweet-sensing gustatory receptor neurons. Furthermore, sweet gustatory receptors such as Gr5a, Gr61a, and Gr64a-f modulate attractive responses. These genetic defects were confirmed using binary food choice assays as well as electrophysiology in the labellum. Taken together, our findings demonstrate that at least two different kinds of receptors are required to discriminate attractive carboxylic acids from other acids.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.4
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• pp.645-653
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• 2003

Taste receptor cells respond to gustatory stimuli using a complex arrangement of receptor molecules, signaling cascades and ion channels. When stimulated, these cells produce action potentials that result in the release of neurotransmitter onto an afferent nerve fiber that in turn relays the identity and intensity of the gustatory stimuli to tie brain. A variety of mechanisms are used in transducing the four primary tastes. Direct interaction of the stimuli with ion channels appears to be of particular importance in transducing stimuli reported as salty or sour, whereas tile second messenger systems cyclic AMP and inositol trisphosphate are important in transducing bitter and sweet stimuli. In addition to the four basic tastes, specific mechanisms exist for the amino acid glutamate, which is sometimes termed the fifth primary taste. The emerging picture is that not only do individual taste qualities use more than one mechanism, but multiple pathways are available for individual tastants as well.

• Molecules and Cells
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• v.40 no.10
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• pp.787-795
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• 2017

Avoiding ingestion of excessively salty food is essential for cation homeostasis that underlies various physiological processes in organisms. The molecular and cellular basis of the aversive salt taste, however, remains elusive. Through a behavioral reverse genetic screening, we discover that feeding suppression by $Na^+$-rich food requires Ionotropic Receptor 76b (Ir76b) in Drosophila labellar gustatory receptor neurons (GRNs). Concentrated sodium solutions with various anions caused feeding suppression dependent on Ir76b. Feeding aversion to caffeine and high concentrations of divalent cations and sorbitol was unimpaired in Ir76b-deficient animals, indicating sensory specificity of Ir76b-dependent $Na^+$ detection and the irrelevance of hyperosmolarity-driven mechanosensation to Ir76b-mediated feeding aversion. Ir76b-dependent $Na^+$-sensing GRNs in both L- and s-bristles are required for repulsion as opposed to the previous report where the L-bristle GRNs direct only low-$Na^+$ attraction. Our work extends the physiological implications of Ir76b from low-$Na^+$ attraction to high-$Na^+$ aversion, prompting further investigation of the physiological mechanisms that modulate two competing components of $Na^+$-evoked gustation coded in heterogeneous Ir76b-positive GRNs.

• International Journal of Oral Biology
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• v.30 no.3
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• pp.91-98
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• 2005

Gamma-aminobutyric acid (GABA) is known as an inhibitory neurotransmitter in the neurons of the central nervous system. However, its detailed action mechanisms in the rostral gustatory zone of the nucleus tractus solitarius (rNTS) have not been established. The present study was aimed to investigate the distribution, role and action mechanisms of GABA in rNTS. Membrane potentials were recorded by whole cell recordings in isolated brain slices of the rat medulla. Superfusion of GABA resulted in a concentration-dependent reduction in input resistance in the neurons in rNTS. The change in input resistance ws accompanied by response to a depolarizing pulse were diminished by GABA. Superfusion of the slices with either $GABA_A$ agonist, muscimol, $GABA_B$ agonist, baclofen or $GABA_C$ agonist, TACA, decreased input resistance and reduced the nerve activity in association with membrane hyperpolarization. It is suggested that inhibitory signals playa role in sensory processing by the rNTS, in that GABA actions occur through activation of $GABA_A,\;GABA_B\;and\;GABA_C$ receptor. These results suggest that GABA has an inhibitory effect on the rNTS through an activation of $GABA_A,\;GABA_B\;and\;GABA_C$ receptors and that the GABAergic inhibition probably plays an important role in sensory processing by the rNTS.

• Journal of Sensor Science and Technology
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• v.22 no.4
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• pp.281-285
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• 2013

In this study a biosensor was developed by using Drosophila cells expressing a gustatory receptor Gr5a and an ion sensitive field effect transistors (ISFETs) sensor device, which demonstrated significant compatibility with the Drosophila cells expressing Gr5a and their response to sugar. These results suggested that the newly developed cell based biosensor has a potential as a simple and easy screening device for Alzheimer's disease in the future.