Structure–Activity Relationship of a Broad-Spectrum Insect Odorant Receptor Agonist

Taylor, Robert W.; Romaine, Ian; Liu, Chao; Murthi, Poornima; Jones, Patrick L.; Waterson, Alex G.; Sulikowski, Gary A.; Zwiebel, Laurence J.

doi:10.1021/cb300331z

Cited by 65 publications

(69 citation statements)

References 19 publications

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“…8-Bromo-cAMP was obtained from Sigma-Aldrich, Inc. (Cat# B5386). VUAA-class compounds were prepared as previously described (8,31,32). All other compounds were obtained from Sigma-Aldrich at the highest purity available.…”

Section: Methodsmentioning

confidence: 99%

“…Responses were scored by post hoc examination of video clips in a double-blinded fashion (Movie S1). The stimuli used in these assays were comprised of a range of unitary odorants as well as highly specific Orco modulators that have been recently characterized (8,31,32). Flagellar beating responses were significantly elevated in the presence of two Orco agonists, VUAA1 and VUAA4, but not in the presence of identical concentrations of a nonpotent structural analog, VUAA0 (32) (Fig.…”

Section: Significancementioning

confidence: 99%

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Odorant receptor-mediated sperm activation in disease vector mosquitoes

Pitts

Liu

Zhou

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Insects, such as the malaria vector mosquito, Anopheles gambiae, depend upon chemoreceptors to respond to volatiles emitted from a range of environmental sources, most notably blood meal hosts and oviposition sites. A subset of peripheral signaling pathways involved in these insect chemosensory-dependent behaviors requires the activity of heteromeric odorant receptor (OR) ion channel complexes and ligands for numerous A. gambiae ORs (AgOrs) have been identified. Although AgOrs are expressed in nonhead appendages, studies characterizing potential AgOr function in nonolfactory tissues have not been conducted. In the present study, we explore the possibility that AgOrs mediate responses of spermatozoa to endogenous signaling molecules in A. gambiae. In addition to finding AgOr transcript expression in testes, we show that the OR coreceptor, AgOrco, is localized to the flagella of A. gambiae spermatozoa where Orco-specific agonists, antagonists, and other odorant ligands robustly activate flagella beating in an Orco-dependent process. We also demonstrate Orco expression and Orco-mediated activation of spermatozoa in the yellow fever mosquito, Aedes aegypti. Moreover, we find Orco localization in testes across distinct insect taxa and posit that OR-mediated responses in spermatozoa may represent a general characteristic of insect reproduction and an example of convergent evolution.transcriptomics | cell signaling | gamete | chemical ecology | Culicidae

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Section: Methodsmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

Odorant receptor-mediated sperm activation in disease vector mosquitoes

Pitts

Liu

Zhou

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…A major issue with the efficacy of VUAA1, however, is that the molecule is not particularly volatile, rendering it largely impotent for insect control. There has therefore been a concerted effort to identify other modulators of Orco, with additional agonists (Chen and Luetje, 2012;Taylor et al, 2012;Romaine et al, 2014), and antagonists Luetje, 2012, 2013;Jones et al, 2012;Pask et al, 2013;Bobkov et al, 2014) now described, with some displaying higher potency and/or volatility than VUAA1. In contrast to the Orco agonists that interfere with odor-guided behaviors by over-stimulating insect olfaction, the antagonists, in principle, would render insects anosmic, preventing any communication via odorants.…”

Section: Targeting the General Insect Sense Of Smellmentioning

confidence: 99%

Pest Control Compounds Targeting Insect Chemoreceptors: Another Silent Spring?

Andersson

Newcomb

2017

Front. Ecol. Evol.

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An emerging concept in the ongoing battle against insect pests is that compounds that influence the behavior of insects by modulating their ability to smell could be developed by targeting their chemoreceptors. This idea was identified by the annual horizon scan of global conservation issues as a topic of concern for their 2015 report. Unfortunately, the publication could only afford a short discussion of the pros and cons of the approach. Here we review the concept and discuss how it might be best implemented to avoid potential off-target effects and environmental harm. We describe the first of this class of compounds, VUAA1, outlining that its highly broad range of potential insect targets would lead to many of the issues associated with broad-spectrum insecticides. We also review compounds and approaches targeting the relatively less conserved carbon dioxide receptor complex and finally highly tuned receptors to conclude that focusing on species-specific pheromone receptors would result in fewer potential off-target effects.

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“…The team's initial behavioral tests suggest that mosquitoes are extremely averse to the molecule. Zwiebel's group has since modified VUAA1 to produce even more potent and effective formulations (7).…”

Section: Multi-pronged Attackmentioning

confidence: 99%

How do mosquitoes smell us? The answers could help eradicate disease

Shen¹

2017

Proc. Natl. Acad. Sci. U.S.A.

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Structure–Activity Relationship of a Broad-Spectrum Insect Odorant Receptor Agonist

Cited by 65 publications

References 19 publications

Odorant receptor-mediated sperm activation in disease vector mosquitoes

Odorant receptor-mediated sperm activation in disease vector mosquitoes

Pest Control Compounds Targeting Insect Chemoreceptors: Another Silent Spring?

How do mosquitoes smell us? The answers could help eradicate disease

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