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Scholarly Works (4 results)

  • Thesis
  • Peer Reviewed
UC Riverside Electronic Theses and Dissertations (2014)

Female mosquitoes have evolved multiple strategies to find hosts from a distance by their odor. Few compounds from the human odor blend are known that mediate these behaviors. One is carbon dioxide (CO2), which activates resting mosquitoes and triggers upwind flight. CpA neurons on the maxillary palps express three members of the gustatory receptor (GR) family and detect CO2.

I found that CO2-sensitive cpA neurons in both Aedes aegypti and Anopheles gambiae also detect components of the human odor blend. CpA responses to these odorants closely resemble its responses to CO2, and when CO2 and skin odorants are presented together, cpA responds more strongly to the combination than to either alone. CpA also detects the natural human odor blend. A novel long-term inhibitor of cpA was used to block cpA activity, and behavioral tests in cpA-off mosquitoes revealed specific deficits in behavioral activation in response to odor, even without a CO2 stimulus.

Genes for the receptor subunits Gr1, 2, and 3 were cloned and expressed in the Drosophila ab1C neuron. In mutants lacking Drosophila receptors, Gr2 and Gr3 form a functional receptor that is as sensitive to CO2 and more sensitive to other odorants than when Gr1 is added. Two inhibitors reduced CO2 responses in neurons expressing Gr2+3, and adding Gr1 modulated their activity in an odorant-specific manner. When mosquito GRs are expressed with Drosophila GRs, they form a CO2 receptor only when both mosquito Gr1+2 and Drosophila Gr63a are present, providing clues to the evolutionary history of protein interactions in this receptor class.

Mosquitoes use odor to discriminate between more and less preferred hosts. Human participants were ranked in attractiveness in wild type and mutant mosquitoes lacking function in cpA or other olfactory neurons. Mutants had altered preferences from wild type. Additional studies may elucidate the mechanisms by which these receptors contribute to preference.

The results of this study integrate molecular, physiological, and behavioral experiments to decode more of the links between a mosquito's chemical environment and her behavioral output. Better understanding the mechanisms driving host-seeking behavior will contribute to critically needed new strategies for combating mosquito-borne disease.

    Cover page: Gustatory Receptors in Mosquito Olfaction and Host-Seeking Behavior
    • Article
    • Peer Reviewed
    UC Riverside Previously Published Works (2020)
    The CO2 receptor in mosquitoes is broadly tuned to detect many diverse odorants. The receptor consists of three subunits (Gr1, Gr2, and Gr3) in mosquitoes but only two subunits in Drosophila: Gr21a (Gr1 ortholog) and Gr63a (Gr3 ortholog). We demonstrate that Gr21a is required for CO2 responses in Drosophila, as has been shown for Gr63a. Next, we generate a Drosophila double mutant for Gr21a and Gr63a, and in this background, we functionally express combinations of Aedes Gr1, Gr2, and Gr3 genes in the CO2 empty neuron. Only two subunits, Gr2 and Gr3, suffice for response to CO2. Addition of Gr1 increases sensitivity to CO2, whereas it decreases the response to pyridine. The inhibitory effect of the antagonist isobutyric acid is observed upon addition of Gr1. Gr1 therefore increases the diversity of ligands of the receptor and modulates the response of the receptor complex.
      Cover page: Contributions of the Conserved Insect Carbon Dioxide Receptor Subunits to Odor Detection
      • Article
      • Peer Reviewed
      UC Riverside Previously Published Works (2019)
      AbstractThe CO2 receptor in mosquitoes is broadly tuned to detect many diverse odorants. The receptor consists of three 7-TM subunits (Gr1, Gr2, and Gr3) in mosquitoes but only two subunits in Drosophila: Gr21a (Gr1 ortholog) and Gr63a (Gr3 ortholog). We demonstrate that Gr21a is required for CO2 responses in Drosophila as has been shown for Gr63a. Next, we generate a Drosophila double mutant for Gr21a and Gr63a, and in this background we functionally express combinations of Aedes Gr1, 2, and 3 genes in the “CO2 empty neuron.” Only two subunits, Gr2 and Gr3, suffice for response to CO2. Addition of Gr1 increases sensitivity to CO2 while it decreases the response to pyridine. The inhibitory effect of the antagonist isobutyric acid is observed upon addition of Gr1. Gr1 therefore increases the diversity of ligands of the receptor, and also modulates the response of the receptor complex.
        • Article
        • Peer Reviewed
        UC Riverside Previously Published Works (2013)
        Female mosquitoes that transmit deadly diseases locate human hosts by detecting exhaled CO2 and skin odor. The identities of olfactory neurons and receptors required for attraction to skin odor remain a mystery. Here, we show that the CO2-sensitive olfactory neuron is also a sensitive detector of human skin odorants in both Aedes aegypti and Anopheles gambiae. We demonstrate that activity of this neuron is important for attraction to skin odor, establishing it as a key target for intervention. We screen ~0.5 million compounds in silico and identify several CO2 receptor ligands, including an antagonist that reduces attraction to skin and an agonist that lures mosquitoes to traps as effectively as CO2. Analysis of the CO2 receptor ligand space provides a foundation for understanding mosquito host-seeking behavior and identifies odors that are potentially safe, pleasant, and affordable for use in a new generation of mosquito control strategies worldwide.
          Cover page: Targeting a Dual Detector of Skin and CO2 to Modify Mosquito Host Seeking
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