Farnesol-Detecting Olfactory Neurons in Drosophila

The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 03/2014; 34(11):3959-68. DOI: 10.1523/JNEUROSCI.4582-13.2014
Source: PubMed


We set out to deorphanize a subset of putative Drosophila odorant receptors expressed in trichoid sensilla using a transgenic in vivo misexpression approach. We identified farnesol as a potent and specific activator for the orphan odorant receptor Or83c. Farnesol is an intermediate in juvenile hormone biosynthesis, but is also produced by ripe citrus fruit peels. Here, we show that farnesol stimulates robust activation of Or83c-expressing olfactory neurons, even at high dilutions. The CD36 homolog Snmp1 is required for normal farnesol response kinetics. The neurons expressing Or83c are found in a subset of poorly characterized intermediate sensilla. We show that these neurons mediate attraction behavior to low concentrations of farnesol and that Or83c receptor mutants are defective for this behavior. Or83c neurons innervate the DC3 glomerulus in the antennal lobe and projection neurons relaying information from this glomerulus to higher brain centers target a region of the lateral horn previously implicated in pheromone perception. Our findings identify a sensitive, narrowly tuned receptor that mediates attraction behavior to farnesol and demonstrates an effective approach to deorphanizing odorant receptors expressed in neurons located in intermediate and trichoid sensilla that may not function in the classical "empty basiconic neuron" system.

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    • "Or23a and Or83c as well as Or2a, Or19a and Or43a were initially described as being expressed in the trichoid sensilla at2 and at3 [7]. Ronderos et al.[32] describe Or23a and Or83c OSNs as being housed in an intermediate sensillum and thus rename at2 to ai2. "
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    ABSTRACT: Odors elicit complex patterns of activated olfactory sensory neurons. Knowing the complete olfactome, i.e. responses in all sensory neurons for all odorants, is desirable to understand olfactory coding. The DoOR project combines all available Drosophila odorant response data into a single consensus response matrix. Since its first release many studies were published: receptors were deorphanized and several response profiles were expanded. In this study, we add to the odor-response profiles for four odorant receptors (Or10a, Or42b, Or47b, Or56a). We deorphanize Or69a, showing a broad response spectrum with the best ligands including 3-hydroxyhexanoate, alpha-terpineol, 3-octanol and linalool. We include these datasets into DoOR, and provide a comprehensive update of both code and data. The DoOR project has a web interface for quick queries (, and a downloadable, open source toolbox written in R, including all processed and original datasets. DoOR now gives reliable odorant-responses for nearly all Drosophila olfactory responding units, listing 693 odorants, for a total of 7381 data points.
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    • "79 tested at low concentrations , probably reflecting those typically encountered by the 176 insect in their environment ( Mathew et al . , 2013 ) . Dedicated OSN circuits have also been 177 identified in Drosophila for geosmin ( DmOr56a ( Stensmyr et al . , 2012 ) ) , citrus terpenes 178 ( DmOr19a ( Dweck et al . , 2013 ) ) , farnesol ( DmOr83c ( Ronderos et al . , 2014 ) ) , polyphenolics 179 ( Dweck et al . , 2015b ) , and for pheromones ( DmOr47b , DmOr67d , and DmOr88a ( Dweck et 180 al . , 2015a ; Ha and Smith , 2006 ) ) . Boyle et al . ( 2013 ) used a computational approach to 181 explore the pharmacophore space of OrXs predicting ~ 500 new activators and inhibitors for 182 each of nine DmOrXs . "
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    ABSTRACT: Insects have co-opted a unique family of seven transmembrane proteins for odour sensing. Odorant receptors are believed to have evolved from gustatory receptors somewhere at the base of the Hexapoda and have expanded substantially to become the dominant class of odour recognition elements within the Insecta. These odorant receptors comprise an obligate co-receptor, Orco, and one of a family of highly divergent odorant “tuning” receptors. The two subunits are thought to come together at some as-yet unknown stoichiometry to form a functional complex that is capable of both ionotropic and metabotropic signalling. While there are still no 3D structures for these proteins, site-directed mutagenesis, resonance energy transfer, and structural modelling efforts, all mainly on Drosophila odorant receptors, are beginning to inform hypotheses of their structures and how such complexes function in odour detection. Some of the loops, especially the second extracellular loop that has been suggested to form a lid over the binding pocket and the extracellular regions of some transmembrane helices, especially the third and to a less extent the sixth and seventh, have been implicated in ligand recognition in tuning receptors. The possible interaction between Orco and tuning receptor subunits through the final intracellular loop and the adjacent transmembrane helices is thought to be important for transducing ligand binding into receptor activation. Potential phosphorylation sites and a calmodulin binding site in the second intracellular loop of Orco are also thought to be involved in regulating channel gating. A number of new methods have recently been developed to express and purify insect odorant receptor subunits in recombinant expression systems. These approaches are enabling high throughput screening of receptors for agonists and antagonists in cell-based formats, as well as producing protein for the application of biophysical methods to resolve the 3D structure of the subunits and their complexes.
    Insect Biochemistry and Molecular Biology 09/2015; 66. DOI:10.1016/j.ibmb.2015.09.010 · 3.45 Impact Factor
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    • "sed from the peal of citrus fruit ( Ronderos et al . , 2014 ) . In contrast to the OR19a pathway , activation of farnesol - sensitive OSNs induces attraction . This might suggest two distinct pathways of which one ( via OR83c ) is essential for citrus attraction and the other ( via OR19a ) for citrus oviposition preference ( Dweck et al . , 2013 ; Ronderos et al . , 2014 ) . However , the ecological significance of farnesol and the OR83c pathway was recently questioned by Mansourian and Stensmyr ( 2015 ) . Farnesol is present in minor quantities only in some citrus varieties , and the fact that the projection neurons from the glomerulus that receives input from Or83c expressing OSNs terminate in the bra"
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    ABSTRACT: Insects detect odorants primarily using odorant receptors (OR) housed in the dendritic membrane of olfactory sensory neurons (OSN). Pioneering studies indicated that insects, like mammals, detect odorants in a combinatorial fashion with a specific odor ligand activating several broadly tuned ORs, and each OR being activated by several ligands. Several recent studies, however, challenge this view by providing examples where ecologically relevant odorants are detected by high-specificity ORs activating dedicated neuronal circuits. Here we review these contrasting findings on the ligand selectivity of insect ORs and their neuronal wiring, and outline scenarios describing how adaptive and neutral evolution might shape both narrow and broad receptor tuning. The fact that not all ORs display narrow tuning might partly be due to key ligands having been missed from screens or too high stimuli concentrations being used. However, the birth-and-death model of OR evolution, involving both adaptive and neutral events, could also explain the evolution of broad tuning in certain receptors due to positive selection or relaxed constraint. If the insect olfactory system indeed contains both narrowly and broadly tuned ORs, this suggests that it is a hybrid between dedicated channels and combinatorial coding. The relative extent of the two coding modes is then likely to differ between species, depending on requirements of perceived chemical space and the size of the OR repertoire. We address this by outlining scenarios where certain insect groups may be more likely to have evolved combinatorial coding as their dominant coding strategy. Combinatorial coding may have evolved predominantly in insects that benefit from the ability to discriminate between a larger number of odorants and odor objects, such as polyphagous or social species. Alternatively, combinatorial coding may have evolved simply as a mechanism to increase perceived odor space in species with small OR repertoires.
    05/2015; 3:53. DOI:10.3389/fevo.2015.00053
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