How Do Bugs Smell?

Abstract

Two papers published this week report both clarifying and somewhat contradictory findings regarding signaling by insect odorant receptors. Odorant receptors (ORs) in mammals are canonical heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) and are often coupled to generation of the second messenger adenosine 3′,5′-monophosphate (cAMP), which can modulate conductance of ion channels. Insect ORs have presented a puzzle, however, as they only vaguely resemble GPCRs and assemble as heterodimers of one variable OR and a common co-receptor called Or83b. Wicher et al . expressed Drosophila receptors Or22a and Or83b in human embryonic kidney cells and used patch clamping to characterize odorant-induced ion currents in the transfected cells. They report that expression of Or83b alone conferred a nonselective cation channel whose conductance was increased by cAMP or guanosine 3′,5′-monophosphate (cGMP). When the authors transfected cells with the Or22a-Or83b pair and also with known mammalian cyclic nucleotide-gated channels, odorant-induced activation of the mammalian channel indicated that the insect OR activated cAMP signaling. Thus, they conclude that the insect ORs themselves form ligand-gated ion channels that sense odorant and amplify signals by G-protein signaling. Sato et al . used similar strategies to analyze various insect ORs. Human cells expressing receptor proteins from fruit fly, mosquito, or silk moth showed a response to odorant that included Ca 2+ influx and increased nonselective cation conductance. Outside-out patch clamp studies from membranes of oocytes or human cells expressing the receptor proteins confirmed that the insect ORs themselves conferred the observed currents. However, Sato et al .’s experiments did not detect odorant-induced generation of cAMP, and pharmacological inhibition of G-protein signaling failed to block odorant-induced currents. As noted in commentary from Chesler and Firestein, resolution of the discrepancies will require further work but may have to do with Sato et al .’s focus on early events (within seconds) and Wicher et al .’s characterization of later events—30 seconds to a minute after receptor stimulation. Insect ORs do not resemble known ion channels at all, so the work suggests there is more to learn about such proteins and raises the question of whether orphan GPCRs in other organisms might also function as ligand-gated ion channels. K. Sato, M. Pellegrino, T. Nakagawa, T. Nakagawa, L. B. Vosshall, K. Touhara, Insect olfactory receptors are heteromeric ligand-gated ion channels. Nature 452 , 1002-1006 (2008). [PubMed] D. Wicher, R. Schäfer, R. Bauernfeind, M. C. Stensmyr, R. Heller, S. H. Heinemann, B. S. Hannson, Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels. Nature 452 , 1007-1011 (2008). [PubMed] A. Chesler, S. Firestein, Current views on odour receptors. Nature 452 , 944 (2008). [PubMed]