Atypical Membrane Topology and Heteromeric Function of Drosophila Odorant Receptors In Vivo

By Richard Benton, Silke Sachse, Stephen W. Michnick, Leslie B. Vosshall. PLoS Biology, 2006

993 citations recorded by the source corpus.

Drosophila olfactory sensory neurons (OSNs) each express two odorant receptors (ORs): a divergent member of the OR family and the highly conserved, broadly expressed receptor OR83b. OR83b is essential for olfaction in vivo and enhances OR function in vitro, but the molecular mechanism by which it acts is unknown. Here we demonstrate that OR83b heterodimerizes with conventional ORs early in the endomembrane system in OSNs, couples these complexes to the conserved ciliary trafficking pathway, and is essential to maintain the OR/OR83b complex within the sensory cilia, where odor signal transduction occurs. The OR/OR83b complex is necessary and sufficient to promote functional reconstitution of odor-evoked signaling in sensory neurons that normally respond only to carbon dioxide. Unexpectedly, unlike all known vertebrate and nematode chemosensory receptors, we find that Drosophila ORs and OR83b adopt a novel membrane topology with their N-termini and the most conserved loops in the cytoplasm. These loops mediate direct association of ORs with OR83b. Our results reveal that OR83b is a universal and integral part of the functional OR in Drosophila. This atypical heteromeric and topological design appears to be an insect-specific solution for odor recognition, making the OR/OR83b complex an attractive target for the development of highly selective insect repellents to disrupt olfactory-mediated host-seeking behaviors of insect disease vectors.

Subfields: Cellular and Molecular Neuroscience, Genetics, Sensory Systems

View Paper: https://www.semanticscholar.org/paper/80038e55f21ea59ff6a54dcb14bc1496fce0d882

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Citations in the corpus

Amino acid coevolution reveals three-dimensional structure and functional domains of insect odorant receptors (2015, positive): “However, insect ORs have the opposite membrane orientation to GPCRs and function as heteromeric complexes (of unknown stoichiometry) of an odour ligand-specific “tuning” OR and a co-receptor, ORCO (formerly called OR83b) 13-16 .”
Uncovering the novel characteristics of Asian honey bee, Apis cerana, by whole genome sequencing (2015, background): “Insects have a number of variable Ors, which form a chaperone with olfactory receptor co-receptor (Orco) in vivo [82-85].”
Variant ionotropic glutamate receptors as chemosensory receptors in Drosophila. (2009, positive): “These proteins contain seven predicted transmembrane domains but are evolutionarily unrelated to GPCRs (Vosshall et al., 1999; Benton et al., 2006; Wistrand et al., 2006) and adopt a distinct membrane topology (Benton et al., 2006; Lundin et al., 2007).”
Olfactory information processing in Drosophila. (2009, neutral): “These seven transmembrane receptors appear to form a novel insect-specific protein family, whose membrane topology is inverted compared with the G protein-coupled receptor superfamily that includes vertebrate odorant receptors [10].”
Molecular architecture of smell and taste in Drosophila. (2007, background): “In vertebrates, each ORN expresses only a single OR allele (Malnic et al. 1999), whereas in flies each ORN expresses one conventional ligand-binding OR and the atypical receptor, Or83b (Vosshall et al. 2000, Larsson et al. 2004, Benton et al. 2006).”
Evolution of insect olfaction. (2011, positive): “Members of this superfamily essentially share no homology to any known gene family, and encodes for seven transmembrane-domain receptors with an inverted transmembrane topology as compared to the G protein-coupled olfactory receptors of vertebrates (Benton et al., 2006).”
Ancient Protostome Origin of Chemosensory Ionotropic Glutamate Receptors and the Evolution of Insect Taste and Olfaction (2010, background): “, as well as to the pairing of ligand-specific ORs with the common OR83b co-receptor”
The evolution of animal chemosensory receptor gene repertoires: roles of chance and necessity (2008, background): “Insect CRs have a seven-transmembrane region similar to vertebrate CRs, but their membrane topology is inverted compared with that of classic GPCRs, such that the N-terminal tail of the insect CR is found in the intracellular regio”
Non-Canonical Odor Coding in the Mosquito (2020, background): “, 2008) that are formed by a heteromultimeric complex of the conserved co-receptor Orco and a ligand-sensitive OR (Benton et al., 2006; Larsson et al., 2004; Neuhaus et al., 2005; Sato et al., 2008).”
The chemoreceptor superfamily in the honey bee, Apis mellifera: expansion of the odorant, but not gustatory, receptor family. (2006, background): “Drosophila olfactory receptor neurons (ORNs) generally express a single olfactory receptor protein (Or; in addition to the widely-expressed conserved DmOr83b), and each ORN expressing a particular Or converges on a single gomerulus in each antennal lobe, thereby allowing for a map of differential ac”
Complementary Function and Integrated Wiring of the Evolutionarily Distinct Drosophila Olfactory Subsystems (2011, background): “DOI:10.1523/JNEUROSCI.2360-11.2011 Copyright © 2011 the authors 0270-6474/11/3113357-19$15.00/0 unrelated to GPCRs (Benton et al., 2006), IRs have derived from ionotropic glutamate receptors (iGluRs) and are found across the protostomian branch of the animal kingdom (Croset et al., 2010).”