Ionotropic Receptors (IRs): Chemosensory ionotropic glutamate receptors in Drosophila and beyond
Graphical abstract
Highlights
► Ionotropic Receptors are chemoreceptors related to ionotropic glutamate receptors. ► IR expression, structure and function is comprehensively described in Drosophila. ► Comparative genomics reveals the origin and diversification of IRs in insects.
Introduction
In 1999, the discovery of Odorant Receptor (OR) genes in the fruit fly, Drosophila melanogaster, allowed definition of the molecular logic of insect olfactory system organization, permitted the development of genetic tools to visualize and manipulate specific olfactory pathways to determine how odors are encoded to evoke behavior, and founded comparative molecular evolutionary studies of the olfactory system across insects (Benton, 2007; Hansson and Stensmyr, 2011; Masse et al., 2009; Su et al., 2009; Vosshall and Stocker, 2007).
During the following decade, comprehensive anatomical and functional maps of Olfactory Sensory Neurons (OSNs) in both the peripheral sensory organs (the third antennal segment [hereafter, antenna] and maxillary palp) and the primary olfactory center in the brain (the antennal lobe) of Drosophila (Su et al., 2009; Vosshall and Stocker, 2007), revealed a large number of antennal neurons that do not express OR genes, or the related Gustatory Receptor (GR) genes (Montell, 2009; Vosshall and Stocker, 2007), implying the existence of another family of insect olfactory receptors. In 2009, through a bioinformatic and expression screen for novel olfactory genes (Benton et al., 2007), a large and highly divergent family of ionotropic glutamate receptor (iGluR)-related genes, named Ionotropic Receptors (IRs), was proposed as the “missing” receptor repertoire (Benton et al., 2009).
In the past four years, characterization of Drosophila IRs, the neuronal circuits in which they function, and their homologs in other species, have revealed them to be an important and ancient repertoire of chemosensory receptors. Here, we synthesize these studies to provide a view of the current knowledge and open questions on the IRs.
Section snippets
IR expression in the Drosophila olfactory system
The Drosophila antenna is covered with porous sensory hairs, or sensilla, of three morphological classes – basiconic, trichoid and coeloconic – which house the ciliated dendritic endings of 1–4 OSNs (Fig. 1A). All basiconic and trichoid OSNs (as well as all maxillary palp OSNs) express OR genes, with the exception of the GR21a/GR63a CO2-sensing neurons (Couto et al., 2005; Fishilevich and Vosshall, 2005; Jones et al., 2007; Kwon et al., 2007; Su et al., 2009; Vosshall and Stocker, 2007). By
Odor-response properties of IR-expressing neurons
Odor ligands for IR-expressing OSNs have been characterized by screening panels of monomolecular odors by extracellular electrophysiological recordings in coeloconic sensilla (Silbering et al., 2011; Yao et al., 2005). Although this technique is relatively rapid, reliable spike-sorting of the 2 or 3 neurons housed in individual sensilla is difficult due to their similar spike amplitudes. Optical imaging of odor-evoked responses of specific IR OSN populations in the antennal lobe, by using IR
Molecular mechanism of IR function
The homology of IRs to iGluRs has facilitated dissection of the mechanism by which these olfactory receptors localize to OSN sensory cilia, recognize odors and produce neuronal depolarization, because of the deep molecular understanding of these synaptic ligand-gated ion channels (Gereau and Swanson, 2008; Mayer, 2011). Like iGluRs, IRs contain a predicted extracellular N-terminus, a bipartite ligand-binding domain (LBD), whose two lobes (S1 and S2) are separated by an ion channel domain, and a
Organization of IR olfactory circuits
The identification of IR genes has also allowed the visualization of the olfactory circuits in which they are expressed, by using IR promoters to drive expression of neuroanatomical markers (Ai et al., 2010; Benton et al., 2009; Silbering et al., 2011). Like OR-expressing OSNs (Couto et al., 2005; Fishilevich and Vosshall, 2005), neurons expressing the same IR converge on a single glomerulus within the antennal lobe, to form a spatial map of sensory input (Fig. 3A). IR-expressing neurons in the
Behaviors mediated by IR olfactory pathways
Two IR pathways have been linked with particular odor-evoked behaviors in Drosophila. First, activity of the acid-sensing IR64a OSNs has been shown to be both necessary and sufficient to promote behavioral aversion (Ai et al., 2010). These neurons may reflect a sensory mechanism that allows flies to avoid unripe or over-fermented rotting fruit.
The second olfactory pathway is that expressing IR84a, which innervates the VL2a glomerulus (Grosjean et al., 2011). VL2a is one of three
IR evolution in drosophilids
While functional studies of IRs and their circuits have focused mostly on D. melanogaster, the wealth of genomic data now available has permitted investigation into the genetic conservation and divergence of these olfactory receptors during evolution at both relatively short and – as considered in Section 8 – long timescales. Within the Drosophila genus, the sequencing of many additional species that have diverse chemical ecology and behavior provide a particularly important resource to examine
IR evolution in insects and beyond
Broader comparative genomic analyses of IR repertoires have provided insights into their evolutionary origin, expansion and diversification (Croset et al., 2010) (Fig. 4A–B). In contrast to the ORs, which are found only in insects, IRs are present in all protostome species examined, but not outside this clade (Fig. 4A). IRs may therefore have evolved in the last common protostome ancestor 550–850 million years ago. Because iGluR-like genes have a broader phylogenetic distribution – present in
Conclusions and perspectives
Since the discovery of IRs, we have learned much about their evolution, expression and function, and about the sensory circuits in which they act. Within insects, IRs appear to define an olfactory subsystem that exhibits many, though not all, of the organizational principles of the OR subsystem. The IR olfactory circuits therefore define a complementary model in which to address both developmental issues of, for example, olfactory receptor gene choice and OSN wiring, and neurobiological
Conflict of interest
The authors declare no conflict of interest.
Acknowledgments
We thank Harald Janovjak, Richard Newcomb and Ana Silbering for discussions and comments on the manuscript. R.R. was supported by the Roche Research Foundation. V.C. was supported by a PhD Fellowship from the Boehringer Ingelheim Fonds. Research in R.B.'s laboratory is supported by the University of Lausanne, a European Research Council Starting Independent Researcher Grant and the Swiss National Science Foundation.
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These authors contributed equally to this work.