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1.  Nutrient sensors 
Current biology : CB  2013;23(9):R369-R373.
PMCID: PMC4332773  PMID: 23660359
2.  Diverse roles for the Drosophila fructose sensor Gr43a 
Fly  2013;8(1):19-25.
The detection of nutrients, both in food and within the body, is crucial for the regulation of feeding behavior, growth, and metabolism. While the molecular basis for sensing food chemicals by the taste system has been firmly linked to specific taste receptors, relatively little is known about the molecular nature of the sensors that monitor nutrients internally. Recent reports of taste receptors expressed in other organ systems, foremost in the gastrointestinal tract of mammals and insects, has led to the proposition that some taste receptors may also be used as sensors of internal nutrients. Indeed, we provided direct evidence that the Drosophila gustatory receptor 43a (Gr43a) plays a critical role in sensing internal fructose levels in the fly brain. In addition to the brain and the taste system, Gr43a is also expressed in neurons of the proventricular ganglion and the uterus. Here, we discuss the multiple potential roles of Gr43a in the fly. We also provide evidence that its activation in the brain is likely mediated by the neuropeptide Corazonin. Finally, we posit that Gr43a may represent only a precedent for other taste receptors that sense internal nutrients, not only in flies but, quite possibly, in other animals, including mammals.
PMCID: PMC3974889  PMID: 24406333
brain; corazonin; fructose; nutrient sensor; proventriculus; receptor; taste; uterus; valence
3.  A fructose receptor functions as a nutrient sensor in the Drosophila brain 
Cell  2012;151(5):1113-1125.
Internal nutrient sensors play important roles in feeding behavior, yet their molecular structure and mechanism of action are poorly understood. Using Ca2+ imaging and behavioral assays, we show that the Gustatory Receptor 43a functions as a narrowly tuned fructose receptor in taste neurons. Remarkably, GR43a also functions as a fructose receptor in the brain. Interestingly, hemolymph fructose levels are tightly linked to feeding status: after nutritious carbohydrate consumption, fructose levels rise several fold and reach a concentration sufficient to activate GR43a in the brain. By using different feeding paradigms and artificial activation of Gr43a-expressing brain neurons, we show that GR43a is both necessary and sufficient to sense hemolymph fructose and promote feeding in hungry flies, but suppress feeding in satiated flies. Thus, our studies indicate that the Gr43a-expressing brain neurons function as a nutrient sensor for hemolymph fructose and assign opposing valence to feeding experiences in a satiation-dependent manner.
PMCID: PMC3509419  PMID: 23178127
4.  Identification of a Drosophila Glucose Receptor Using Ca2+ Imaging of Single Chemosensory Neurons 
PLoS ONE  2013;8(2):e56304.
Evaluation of food compounds by chemosensory cells is essential for animals to make appropriate feeding decisions. In the fruit fly Drosophila melanogaster, structurally diverse chemicals are detected by multimeric receptors composed of members of a large family of Gustatory receptor (Gr) proteins. Putative sugar and bitter receptors are expressed in distinct subsets of Gustatory Receptor Neurons (GRN) of taste sensilla, thereby assigning distinct taste qualities to sugars and bitter tasting compounds, respectively. Here we report a Ca2+ imaging method that allows association of ligand-mediated responses to a single GRN. We find that different sweet neurons exhibit distinct response profiles when stimulated with various sugars, and likewise, different bitter neurons exhibit distinct response profiles when stimulated with a set of bitter chemicals. These observations suggest that individual neurons within a taste modality are represented by distinct repertoires of sweet and bitter taste receptors, respectively. Furthermore, we employed this novel method to identify glucose as the primary ligand for the sugar receptor Gr61a, which is not only expressed in sweet sensing neurons of classical chemosensory sensilla, but also in two supersensitive neurons of atypical taste sensilla. Thus, single cell Ca2+ imaging can be employed as a powerful tool to identify ligands for orphan Gr proteins.
PMCID: PMC3571953  PMID: 23418550
5.  Hierarchical chemosensory regulation of male-male social interactions in Drosophila 
Nature neuroscience  2011;14(6):757-762.
Pheromones regulate male social behaviors in Drosophila, but the identities and behavioral role(s) of these chemosensory signals, and how they interact, are incompletely understood. Here we show that (Z)-7-tricosene (7-T), a male-enriched cuticular hydrocarbon (CH) previously shown to inhibit male-male courtship, is also essential for normal levels of aggression. The opposite influences of 7-T on aggression and courtship are independent, but both require the gustatory receptor Gr32a. Surprisingly, sensitivity to 7-T is required for the aggression-promoting effect of 11-cis-vaccenyl acetate (cVA), an olfactory pheromone, but 7-T sensitivity is independent of cVA. 7-T and cVA therefore regulate aggression in a hierarchical manner. Furthermore, the increased courtship caused by depletion of male CHs is suppressed by a mutation in the olfactory receptor Or47b. Thus, male social behaviors are controlled by gustatory pheromones that promote and suppress aggression and courtship, respectively, and whose influences are dominant to olfactory pheromones that enhance these behaviors.
PMCID: PMC3102769  PMID: 21516101
6.  Nocturnal Male Sex Drive in Drosophila 
Current biology : CB  2007;17(3):244-251.
Many behaviors and physiological processes including locomotor activity, feeding, sleep, mating, and migration are dependent on daily or seasonally reoccurring, external stimuli [1–3]. In D. melanogaster, one of the best-studied circadian behaviors is locomotion. The fruit fly is considered a diurnal (day active/night inactive) insect, based on locomotor-activity recordings of single, socially naive flies [4, 5]. We developed a new circadian paradigm that can simultaneously monitor two flies in simple social contexts. We find that heterosexual couples exhibit a drastically different locomotor-activity pattern than individual males, females, or homosexual couples. Specifically, male-female couples exhibit a brief rest phase around dusk but are highly active throughout the night and early morning. This distinct locomotor-activity rhythm is dependent on the clock genes and synchronized with close-proximity encounters, which reflect courtship, between the male and female. The close-proximity rhythm is dependent on the male and not the female and requires circadian oscillators in the brain and the antenna. Taken together, our data show that constant exposure to stimuli emanating from the female and received by the male olfactory and other sensory systems is responsible for the significant shift in intrinsic locomotor output of socially interacting flies.
PMCID: PMC2239012  PMID: 17276917
7.  Sugar receptors in Drosophila 
Current biology : CB  2007;17(20):1809-1816.
Detection and discrimination of chemical compounds in potential foods are essential sensory processes when animals feed. The fruit fly Drosophila melanogaster employs 68 different gustatory receptors (GRs) for the detection of mostly non-volatile chemicals that include sugars, a diverse group of toxic compounds present in many inedible plants and spoiled foods, and pheromones [1–6]. With the exception of a trehalose (GR5a) and a caffeine (GR66a) receptor [7–9], the functions of GRs involved in feeding are unknown. Here, we show that the Gr64 genes encode receptors for numerous sugars. We generated a fly strain that contained a deletion for all six Gr64 genes (ΔGr64) and showed that these flies exhibit no or a significantly diminished proboscis extension reflex (PER) response when stimulated with glucose, maltose, sucrose and several other sugars. The only considerable response was detected when Gr64 mutant flies were stimulated with fructose. Interestingly, response to trehalose is also abolished in these flies, even though they contain a functional Gr5a gene, which has been previously shown to encode a receptor for this sugar [8, 9]. This observation indicates that two or more Gr genes are necessary for trehalose detection, suggesting that GRs function as multimeric receptor complexes. Finally, we present evidence that some members of the Gr64 gene family are transcribed as a polycistronic mRNA, providing a mechanism for co-expression of multiple sugar receptors in the same taste neurons.
PMCID: PMC2078200  PMID: 17919910
8.  Taste and pheromone perception in mammals and flies 
Genome Biology  2003;4(7):220.
Comparison of the olfactory systems in Drosophila and mouse uncovers clear differences and a few surprising similarities.
The olfactory systems of insects and mammals have analogous anatomical features and use similar molecular logic for olfactory coding. The molecular underpinnings of the chemosensory systems that detect taste and pheromone cues have only recently been characterized. Comparison of these systems in Drosophila and mouse uncovers clear differences and a few surprising similarities.
PMCID: PMC193622  PMID: 12844351
9.  Multiple RNA-protein interactions in Drosophila dosage compensation 
Genome Biology  2000;1(6):reviews1030.1-reviews1030.5.
From worms to humans, recognizing and modifying a specific chromosome is essential for dosage compensation, the mechanism by which equal X-linked gene expression in males and females is achieved. Recent molecular genetic and biochemical studies have provided new insights into how regulatory factors in Drosophila are recruited and assembled on the X chromosome, leading to the essential hypertranscription of its genes.
PMCID: PMC138894  PMID: 11178270

Results 1-9 (9)