Controversy and consensus: noncanonical signaling mechanisms in the insect olfactory system

Abstract

There is broad consensus that olfactory signaling in vertebrates and the nematode C. elegans uses canonical G-protein-coupled receptor transduction pathways. In contrast, mechanisms of insect olfactory signal transduction remain deeply controversial. Genetic disruption of G proteins and chemosensory ion channels in mice and worms leads to profound impairment in olfaction, while similar mutations in the fly show more subtle phenotypes. The literature contains contradictory claims that insect olfaction uses cAMP, cGMP, or IP3 as second messengers; that insect odorant receptors couple to G(alpha)s or G(alpha)q pathways; and that insect odorant receptors are G-protein-coupled receptors or odor-gated ion channels. Here we consider all the evidence and offer a consensus model for a noncanonical mechanism of olfactory signal transduction in insects.

Figure 1. Insect olfactory sensilla

(A) Adult male vinegar fly, Drosophila melanogaster, on a blade of grass. Black box indicates the position of the chemosensory antennae. Adapted from a royalty-free photo (© Studiotouch #8408777, Fotolia.com). (B) Cartoon of one antenna, with the segments labeled and the position of three different types of chemosensory hairs on the third segment indicated, along with the classes of stimuli that activate neurons in these sensilla. Adapted from [34], published by the Public Library of Science, which uses the Creative Commons Attribution License.

Figure 2. Diverse chemosensory receptors mediating olfaction in insects

(A) Basiconic sensilla are tuned to carbon dioxide detection using Gr21a/Gr63a (not shown) and general odorant detection using OR/OR83b complexes. The general odorant is indicated by the orange dot and interacts with the OR subunit in the complex. (B) Pheromones are detected with distinct OR/OR83b complexes that act in concert with a CD36 homologue called SNMP [44,45]. For the detection of cis-vaccenyl acetate (cVA), a soluble odorant binding protein called LUSH is required [55]. cVA is indicated by the purple ellipse and interacts with the OR67d subunit in the complex. (C) A newly described family of chemosensory receptors is encoded by variant ionotropic receptors (IRs) [46]. IRs are expressed in coeloconic sensilla that detect general odorants, small amines, and humidity. Ligands (indicated by the orange dot) are presumed to be bound by extracellular domains of these receptors, but the nature of the IR receptor complex and what subunit(s) bind ligands remain to be determined.

Figure 3. Models of insect olfactory receptor signal transduction

(A) Canonical G protein signaling in the mammalian olfactory system (ACIII, adenylate cyclase III; CNGC, cyclic nucleotide-gated channel). (B) Sato et al. [51] propose that insect ORs form ligand-gated nonselective cation channels activated rapidly by odors in the absence of G-protein signaling. (C) Wicher et al. [52] propose that the variable ORx subunit is a G protein-coupled receptor and that OR83b is a cyclic nucleotide-gated ion channel. Odor activation of ORx triggers two pathways, a fast short ionotropic pathway and a slow prolonged metabotropic pathway. The metabotropic pathway involves G_s coupling of ORx, leading to the production of intracellular cAMP, which activates OR83b. (D) Integrative model of insect olfactory signal transduction proposed in this review article. See text for details. Abbreviations: CaM, calmodulin; PKC, protein kinase C; PKA, protein kinase A; PKG, protein kinase G; PLC, phospholipase C; AC, adenylate cyclase; GC, guanylate cyclase.