Insect Odorant Response Sensitivity Is Tuned by Metabotropically Autoregulated Olfactory Receptors

Abstract

Insects possess one of the most exquisitely sensitive olfactory systems in the animal kingdom, consisting of three different types of chemosensory receptors: ionotropic glutamate-like receptors (IRs), gustatory receptors (GRs) and odorant receptors (ORs). Both insect ORs and IRs are ligand-gated ion channels, but ORs possess a unique configuration composed of an odorant-specific protein OrX and a ubiquitous coreceptor (Orco). In addition, these two ionotropic receptors confer different tuning properties for the neurons in which they are expressed. Unlike IRs, neurons expressing ORs are more sensitive and can also be sensitized by sub-threshold concentrations of stimuli. What is the mechanistic basis for these differences in tuning? We show that intrinsic regulation of Orco enhances neuronal response to odorants and sensitizes the ORs. We also demonstrate that inhibition of metabotropic regulation prevents receptor sensitization. Our results indicate that Orco-mediated regulation of OR sensitivity provides tunable ionotropic receptors capable of detecting odors over a wider range of concentrations, providing broadened sensitivity over IRs themselves.

Odor induced cAMP production in Drosophila melanogaster olfactory sensory neurons

“…This may reflect the inability of the drug to inhibit ACs completely. Similarly, SQ22536 did not suppress OSN activity at high stimulus concentrations (Getahun et al, 2013). As Or22a…”

“…sensitivity, are regulated by multiple intracellular signaling cascades (Nakagawa and Vosshall, 2009;Wicher, 2015). The second messenger 3′,5′-cyclic adenosine monophosphate (cAMP) is an activating ligand for Orco channels (Wicher et al, 2008;Stengl, 2010;Stengl and Funk, 2013) and has been shown to enhance the activity of olfactory sensory neurons (OSNs) that express ORs (Olsson et al, 2011;Getahun et al, 2013). Insect OSNs possess the cellular machinery required to produce cAMP (Iourgenko and Levin, 2000;Boto et al, 2010) and disruption of this signaling cascade has been reported to affect the functional properties of OSNs (Martín et al, 2001;Gomez-Diaz et al, 2004;Deng et al, 2011).…”

Intracellular regulation of the insect chemoreceptor complex impacts odor localization in flying insects

“…However, little is known about the molecular basis for this sensitivity. Studies have shown that the OrX-Orco complex is subject to metabotropic signalling (Stengl, 1993(Stengl, , 2010Kain et al, 2008;Wicher et al, 2008;Deng et al, 2011;Sargsyan et al, 2011;Getahun et al, 2013;Ignatious Raja et al, 2014;Carraher et al, 2015) and also that OrX-Orco activation enhances secondary messenger production (Wicher, et al, 2008;Miazzi et al, 2016). Neither OrX nor Orco has any obvious homology to known cyclic nucleotide binding domains, and it is not clear how these two proteins interact.…”

Identification and characterization of the bombykal receptor in the hawkmoth Manduca sexta

“…This finding could be explained by different hypotheses. It could be hypothesized that MsexOrs and MsexOrco need to be phosphorylated before they can be gated by BAL as an ionotropic odor receptor-ion channel complex, as suggested previously in D. melanogaster (Sargsyan et al, 2011;Getahun et al, 2013). Alternatively, it could be hypothesized that MsexOrs couple to G αq proteins, requiring activation of PLC for pheromone transduction, as suggested by previous findings in moths and cockroaches (Breer et al, 1990;Boekhoff et al, 1993Boekhoff et al, , 1994; for a review, see Stengl, 2010).…”

“…Next, a possible dependence of the BAL response on PLC or PKC activity was examined, as reported previously for hawkmoth pheromone transduction (Stengl, 1993(Stengl, , 1994(Stengl, , 2010Dolzer et al, 2008) and for fruitfly Orco (Sargsyan et al, 2011;Getahun et al, 2013). Thus, Ca 2+ imaging experiments were performed in HEK293 cells expressing MsexOrco and MsexOr1.…”