Abstract
We previously found that dopamine signaling modulates the sensitivity of wild-type C. elegans to the aversive odorant 1-octanol. C. elegans lacking the CAT-2 tyrosine hydroxylase enzyme, which is required for dopamine biosynthesis, are hypersensitive in their behavioral avoidance of dilute concentrations of octanol. Dopamine can also modulate the context-dependent response of C. elegans lacking RGS-3 function, a negative regulator of Gα signaling. rgs-3 mutant animals are defective in their avoidance of 100% octanol when they are assayed in the absence of food (E. coli bacterial lawn), but their response is restored when they are assayed in the presence of food or exogenous dopamine. However, it is not known which receptor might be mediating dopamine's effects on octanol avoidance. Herein we describe a role for the C. elegans D2-like receptor DOP-3 in the regulation of olfactory sensitivity. We show that DOP-3 is required for the ability of food and exogenous dopamine to rescue the octanol avoidance defect of rgs-3 mutant animals. In addition, otherwise wild-type animals lacking DOP-3 function are hypersensitive to dilute octanol, reminiscent of cat-2 mutants. Furthermore, we demonstrate that DOP-3 function in the ASH sensory neurons is sufficient to rescue the hypersensitivity of dop-3 mutant animals, while dop-3 RNAi knockdown in ASH results in octanol hypersensitivity. Taken together, our data suggest that dopaminergic signaling through DOP-3 normally acts to dampen ASH signaling and behavioral sensitivity to octanol.
Highlights
With the possible exception of insects, olfaction is mediated by G protein-coupled signal transduction pathways across species [1,2,3,4,5,6]
Rgs-3 animals respond significantly better when they are assayed in the presence of food or exogenous dopamine (DA) [13]
Loss of DOP-1, DOP-2 or DOP-4 had no effect on the food rescue of rgs-3 octanol avoidance, while rgs3;dop-3 animals remained defective for octanol avoidance when assayed on food (Figure 1)
Summary
With the possible exception of insects, olfaction is mediated by G protein-coupled signal transduction pathways across species [1,2,3,4,5,6]. Odorant ligands bind to 7-transmembrane G protein-coupled receptors (GPCRs) expressed in olfactory sensory neurons. This binding induces a conformational change in the receptor that activates the associated heterotrimeric G proteins. G protein-coupled pathways in the AWA and AWC chemosensory neurons mediate chemotaxis towards attractive odorants that likely signal the presence of a food source, while the ASH, AWB and ADL neurons detect aversive odorants that might indicate an unfavorable or harmful environment [1]. The well-characterized polymodal ASH sensory neurons detect a wide range of aversive stimuli, including volatile odorants (e.g. octanol), soluble chemicals (e.g. quinine), high osmolarity and the mechanical stimulus of light touch to the nose [7,8,9,10,11]. Animals exhibit an avoidance response by rapidly initiating backwards locomotion upon detection of any of these stimuli
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