Odorant Inhibition in Mosquito Olfaction.
Ontology highlight
ABSTRACT:
SUBMITTER: Xu P
PROVIDER: S-EPMC6660600 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:In vertebrates, odors are thought to be detected by a multigene family encoding several hundreds of seven-transmembrane-domain G-protein-coupled receptors found in fish, rat, mouse, dog, and human. Recently, the putative odorant receptor (OR) gene family in the chicken has been characterized. Twelve members have been isolated and subdivided into six subfamilies. Herein, we have further characterized the chicken olfactory receptor subfamily 7 (COR7) composed of two highly related genes (named COR7a and COR7b) which are 98.5% identical. By in situ hybridization experiments, both COR7a and COR7b transcripts were detected in the olfactory epithelium from embryonic day 6 (E6) to the new born stage. Within the olfactory epithelium, the spatial distribution of COR7a and COR7b labeled cells was random. We also observed that every individual positive cell did not coexpress the COR7a and COR7b genes. Interestingly, the COR7b gene was found to be transiently expressed in the notochord from E2 to E6, whereas COR7a or any of the other known members of the COR gene family were not detected in this mesodermal tissue. These data suggest that, in addition to its potential role as an OR in the olfactory system, COR7b may also have a function in the notochord that is essential for the dorsoventral organization of the neural tube and of the somitic mesoderm. We also discuss the possible role(s) of a putative OR present in both the notochord and the sensory olfactory epithelium.
| S-EPMC20799 | biostudies-literature
Project description:The cell surface metalloprotease ADAM17 and its binding partners iRhom2 and iRhom1 modulate cell-cell interactions by mediating the release of membrane proteins such as TNFa and EGFR-ligands from the cell surface. Most cell types express both iRhoms, though myeloid cells exclusively express iRhom2, and iRhom1 is the main iRhom in the mouse brain. Here we report that iRhom2 is uniquely expressed in olfactory sensory neurons (OSNs), highly specialized cells expressing one olfactory receptor (OR) from a repertoire of over a thousand OR genes in mice. iRhom2-/- mice had no evident morphological defects in the olfactory epithelium (OE), yet RNAseq analysis revealed differential expression of a small subset of ORs. Notably, while the majority of ORs remain unaffected in iRhom2-/- OE, OSNs expressing ORs that are enriched in iRhom2-/- OE showed fewer gene expression changes upon odor environmental changes than the majority of OSNs. Moreover, we discovered an inverse correlation between the expression of iRhom2 compared to OSN activity genes and that odor exposure negatively regulates iRhom2 expression. Given that ORs are specialized G-protein coupled receptors (GPCRs) and many GPCRs activate iRhom2/ADAM17, we investigated if ORs could activate iRhom2/ADAM17. Activation of OR2AT4 by its agonist sandalore in keratinocytes, where this receptor is ectopically expressed, leads to ERK1/2 phosphorylation, likely via an iRhom2/ADAM17-dependent pathway. Taken together, these findings point to a mechanism by which odor stimulation of OSNs activates iRhom2/ADAM17 catalytic activity, resulting in downstream transcriptional changes to the OR repertoire and activity genes, and driving a negative feedback loop to downregulate iRhom2 expression.
2024-05-28 | GSE268171 | GEO
Project description:Insect repellents are important prophylactic tools for travelers and populations living in endemic areas of malaria, dengue, encephalitis, and other vector-borne diseases. DEET (N,N-diethyl-3-methylbenzamide) is a 6-decade-old synthetic repellent, which is still considered the gold standard of mosquito repellents. Mosquitoes use their sense of smell to detect DEET, but there are currently two hypotheses regarding its mode of action: activation of ionotropic receptor IR40a vs. odorant receptor(s). Here, we demonstrate that DEET, picaridin, insect repellent 3535, and p-menthan-3,8-diol activate the odorant receptor CquiOR136 of the southern house mosquito, Culex quinquefasciatus. Electrophysiological and behavioral assays showed that CquiIR40a knockdown had no significant effect on DEET detection and repellency. By contrast, reduction of CquiOR136 transcript levels led to a significant decrease in electroantennographic responses to DEET and a complete lack of repellency. Thus, direct activation of an odorant receptor, not an ionotropic receptor, is necessary for DEET reception and repellency in Culex mosquitoes. Interestingly, methyl jasmonate, a repellent derived from the nonvolatile jasmonic acid in the signaling pathway of plant defenses, elicited robust responses in CquiOR136•CquiOrco-expressing Xenopus oocytes, thus suggesting a possible link between natural products with long insect-plant evolutionary history and synthetic repellents.
| S-EPMC4246313 | biostudies-literature
Project description:The mosquito Anopheles gambiae is the major vector of malaria in sub-Saharan Africa. It locates its human hosts primarily through olfaction, but little is known about the molecular basis of this process. Here we functionally characterize the Anopheles gambiae odorant receptor (AgOr) repertoire. We identify receptors that respond strongly to components of human odour and that may act in the process of human recognition. Some of these receptors are narrowly tuned, and some salient odorants elicit strong responses from only one or a few receptors, suggesting a central role for specific transmission channels in human host-seeking behaviour. This analysis of the Anopheles gambiae receptors permits a comparison with the corresponding Drosophila melanogaster odorant receptor repertoire. We find that odorants are differentially encoded by the two species in ways consistent with their ecological needs. Our analysis of the Anopheles gambiae repertoire identifies receptors that may be useful targets for controlling the transmission of malaria.
| S-EPMC2833235 | biostudies-literature
Project description:BackgroundDEET, 2-undecanone (2-U), IR3535 and Picaridin are widely used as insect repellents to prevent interactions between humans and many arthropods including mosquitoes. Their molecular action has only recently been studied, yielding seemingly contradictory theories including odorant-dependent inhibitory and odorant-independent excitatory activities on insect olfactory sensory neurons (OSNs) and odorant receptor proteins (ORs).Methodology/principal findingsHere we characterize the action of these repellents on two Aedes aegypti ORs, AaOR2 and AaOR8, individually co-expressed with the common co-receptor AaOR7 in Xenopus oocytes; these ORs are respectively activated by the odors indole (AaOR2) and (R)-(-)-1-octen3-ol (AaOR8), odorants used to locate oviposition sites and host animals. In the absence of odorants, DEET activates AaOR2 but not AaOR8, while 2-U activates AaOR8 but not AaOR2; IR3535 and Picaridin do not activate these ORs. In the presence of odors, DEET strongly inhibits AaOR8 but not AaOR2, while 2-U strongly inhibits AaOR2 but not AaOR8; IR3535 and Picaridin strongly inhibit both ORs.Conclusions/significanceThese data demonstrate that repellents can act as olfactory agonists or antagonists, thus modulating OR activity, bringing concordance to conflicting models.
| S-EPMC2920324 | biostudies-literature
Project description:Mosquitoes exhibit highly diverse and fast evolving odorant receptors (ORs). The indole-sensitive OR gene clade, comprised of Or2 and Or10 is a notable exception on account of its conservation in both mosquito subfamilies. This group of paralogous genes exhibits a complex developmental expression pattern in Aedes aegypti: AaegOr2 is expressed in both adults and larvae, AaegOr10 is adult-specific and a third member named AaegOr9 is larva-specific. OR2 and OR10 have been deorphanized and are selectively activated by indole and skatole, respectively. Using the two-electrode voltage clamp of Xenopus oocytes expressing Ae. aegypti ORs, we show that AaegOR9 is supersensitive and narrowly tuned to skatole. Our findings suggest that Ae. aegypti has evolved two distinct molecular strategies to detect skatole in aquatic and terrestrial environments, highlighting the central ecological roles of indolic compounds in the evolutionary and life histories of these insects.
| S-EPMC6353850 | biostudies-literature
Project description:Odorant-dependent behaviors in insects are triggered by the binding of odorant ligands to the variable subunits of heteromeric olfactory receptors. Previous studies have shown, however, that specific odor binding to ORco, the common subunit of odorant receptor heteromers, may allosterically alter olfactory receptor function and profoundly affect subsequent behavioral responses. Using an insect cell-based screening platform, we identified and characterized several antagonists of the odorant receptor coreceptor of the African malaria vector Anopheles gambiae (AgamORco) in a small collection of natural volatile organic compounds. Because some of the identified antagonists were previously shown to strongly repel Anopheles and Culex mosquitoes, we examined the bioactivities of the identified antagonists against Aedes, the third major genus of the Culicidae family. The tested antagonists inhibited the function of Ae. aegypti ORco ex vivo and repelled adult Asian tiger mosquitoes (Ae. albopictus). Binary mixtures of specific antagonists elicited higher repellency than single antagonists, and binding competition assays suggested that this enhanced repellence is due to antagonist interaction with distinct ORco sites. Our results also suggest that the enhanced mosquito repellency by antagonist mixtures is due to additive rather than synergistic effects of the specific antagonist combinations on ORco function. Taken together, these findings provide novel insights concerning the molecular aspects of odorant receptor function. Moreover, our results demonstrate that a simple screening assay may be used for the identification of allosteric modifiers of olfactory-driven behaviors capable of providing enhanced personal protection against multiple mosquito-borne infectious diseases.
| S-EPMC7948460 | biostudies-literature
Project description:BackgroundThe mosquito Anopheles funestus is one of the major malaria vector species in sub-Saharan Africa. Olfaction is essential in guiding mosquito behaviors. Odorant-binding proteins (OBPs) are highly expressed in insect olfactory tissues and involved in the first step of odorant reception. An improved understanding of the function of malaria mosquito OBPs may contribute to identifying new attractants/repellents and assist in the development of more efficient and environmentally friendly mosquito controlling strategies.MethodologyIn this study, a large screening of over 50 ecologically significant odorant compounds led to the identification of 12 ligands that elicit significant electroantennographic (EAG) responses from An. funestus female antennae. To compare the absolute efficiency/potency of these chemicals, corrections were made for differences in volatility by determining the exact amount in a stimulus puff. Fourteen AfunOBP genes were cloned and their expression patterns were analyzed. AfunOBP1, 3, 7, 20 and 66 showed olfactory tissue specificity by reverse transcriptase PCR (RT-PCR). Quantitative real-time PCR (qRT-PCR) analysis showed that among olfactory-specific OBPs, AfunOBP1 and 3 are the most enriched OBPs in female antennae. Binding assay experiments showed that at pH 7, AfunOBP1 significantly binds to 2-undecanone, nonyl acetate, octyl acetate and 1-octen-3-ol but AfunOBP3, which shares 68% identify with AfunOBP1 at amino acid level, showed nearly no binding activity to the selected 12 EAG-active odorant compounds.ConclusionThis work presents for the first time a study on the odorants and OBPs of the malaria vector mosquito An. funestus, which may provide insight into the An. funestus olfactory research, assist in a comparative study between major malaria mosquitoes An. gambiae and An. funestus olfactory system, and help developing new mosquito control strategies to reduce malaria transmission.
| S-EPMC2962654 | biostudies-literature
Project description:Female mosquitoes are major vectors of human disease and the most dangerous are those that preferentially bite humans. A 'domestic' form of the mosquito Aedes aegypti has evolved to specialize in biting humans and is the main worldwide vector of dengue, yellow fever, and chikungunya viruses. The domestic form coexists with an ancestral, 'forest' form that prefers to bite non-human animals and is found along the coast of Kenya. We collected the two forms, established laboratory colonies, and document striking divergence in preference for human versus non-human animal odour. We further show that the evolution of preference for human odour in domestic mosquitoes is tightly linked to increases in the expression and ligand-sensitivity of the odorant receptor AaegOr4, which we found recognizes a compound present at high levels in human odour. Our results provide a rare example of a gene contributing to behavioural evolution and provide insight into how disease-vectoring mosquitoes came to specialize on humans.
| S-EPMC4286346 | biostudies-literature
Project description:The Asian longhorned beetle Anoplophora glabripennis (Motchulsky) is an exotic forest pest that has repeatedly invaded North America and Europe from Asia, and has the potential to kill millions of trees and cause billions of dollars in damage. Traps baited with an attractive mixture of volatile organic compounds from hosts have been of limited success in monitoring invasion sites. We propose that lures might be improved through studying the olfactory system of adult beetles, especially the gene family of odorant receptors (ORs) and the structure of the antennal lobes of the brain. Here, we report identification of 132 ORs in the genome of A. glabripennis (inclusive of one Orco gene and 11 pseudogenes), some of which are orthologous to known pheromone receptors of other cerambycid beetles. We also identified three ORs that are strongly biased toward expression in the female transcriptome, and a single OR strongly biased toward males. Three-dimensional reconstruction of the antennal lobes of adults suggested a male-specific macroglomerulus and several enlarged glomeruli in females. We predict that functional characterization of ORs and glomeruli will lead to identification of key odorants in the life history of A. glabripennis that may aid in monitoring and controlling future invasions.
| S-EPMC5330384 | biostudies-literature