Speaker
Description
A striking dichotomy in olfactory systems exists between mammals, which use G-protein coupled receptors (GPCRs) for odour detection, and insects, which rely on odour-gated ion channels, including the Ionotropic receptor (Ir) repertoire, which is distantly related to synaptic ionotropic glutamate receptor (iGluR) family. Here we report the first evidence for a GPCR signaling pathway in shaping the odour-tuning profile of an insect OSN. Characterisation of the volatile carboxylic acid-sensing properties of Drosophila melanogaster Ir64a neurons revealed two subpopulations: one type (DC4) is broadly-tuned to acids of diverse chain length, while the other (DP1m) is narrowly tuned to short-chain acids. Comparative single-cell transcriptomic analysis of DC4 and DP1m populations revealed a Gγ subunit, Gγ30A, as being more highly expressed in DC4. We show that Gγ30A is required to broaden the acid-tuning profile of DC4 neurons, acting together with the non-differentially expressed Gαs and Gβ13F subunits and the adenylyl cyclase, Ac13E. Screening of candidate GPCRs functioning upstream of this metabotropic signaling pathway identified the Latrophilin-family adhesion GPCR, Cirl, whose vertebrate homologues are best-characterised for roles in synapse assembly. Cirl is broadly transcribed in antennal neurons (including both DC4 and DP1m) but, remarkably, only robustly detected at the protein level in Ir64a DC4 neuron ciliated dendrites, a localisation pattern that requires Gγ30A. Importantly, loss of Cirl is also required for the broad tuning of DC4 neurons towards carboxylic acids, while Cirl and Ir64a are not co-dependent for cilia localisation. We further show that in D. sechellia, a close relative of D. melanogaster with distinct acid preferences, DC4 neurons have reduced breadth of tuning. This interspecific difference cannot be explained by changes in Ir64a sequence nor decreased expression, but is associated with lower expression in D. sechellia of two components of this G protein signaling pathway (Cirl and Ac13E). Together, our work reveals the engagement of a metabotropic pathway with ionotropic signal transduction, revealing an unprecedented mechanism defining olfactory sensory neuron tuning properties. More generally, our work underline further molecular parallels between signalling mechanisms in sensory cilia and central synapses.
