A Family of non-GPCR Chemosensors Defines an Alternative Logic for Mammalian Olfaction

Paul L Greer,Daniel M Bear,Jean-Marc Lassance,Maria Lissitsyna Bloom,Tatsuya Tsukahara,Stan L Pashkovski,Francis Kei Masuda,Alexandra C Nowlan,Rory Kirchner,Hopi E Hoekstra,Sandeep Robert Datta

doi:10.1016/j.cell.2016.05.001

Paul L Greer, Daniel M Bear + Show 9 more

Open Access

https://doi.org/10.1016/j.cell.2016.05.001

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Journal: Cell	Publication Date: May 26, 2016
Citations: 121	License type: publisher-specific-oa

Affiliation: Harvard University, Howard Hughes Medical Institute

Abstract

Odor perception in mammals is mediated by parallel sensory pathways that convey distinct information about the olfactory world. Multiple olfactory subsystems express characteristic seven-transmembrane G-protein-coupled receptors (GPCRs) in a one-receptor-per-neuron pattern that facilitates odor discrimination. Sensory neurons of the "necklace" subsystem are nestled within the recesses of the olfactory epithelium and detect diverse odorants; however, they do not express known GPCR odor receptors. Here, we report that members of the four-pass transmembrane MS4A protein family are chemosensors expressed within necklace sensory neurons. These receptors localize to sensory endings and confer responses to ethologically relevant ligands, including pheromones and fatty acids, invitro and invivo. Individual necklace neurons co-express many MS4A proteins and are activated by multiple MS4A ligands; this pooling of information suggests that the necklace is organized more like subsystems for taste than for smell. The MS4As therefore define a distinct mechanism and functional logic for mammalian olfaction.

Highlights

As animals navigate the natural world, they encounter an unending variety of small molecules, which are rich sources of information that signify the presence of organisms and salient objects in the environment
The olfactory system detects many of these molecules through odorant receptor proteins expressed by peripheral olfactory sensory neurons (OSNs), which are coupled to higher brain circuits mediating odor perception (Axel, 1995; Ihara et al, 2013)
This pattern of expression defines specific information channels in the olfactory system, as the axons of those sensory neurons that express the same odorant receptor converge on a small number of insular structures within the olfactory bulb called glomeruli; these glomeruli are differentially recruited as animals sense distinct smells, enabling the brain to discriminate odors detected by the nose (Mori and Sakano, 2011)

Summary

Introduction

As animals navigate the natural world, they encounter an unending variety of small molecules, which are rich sources of information that signify the presence of organisms and salient objects in the environment. The main and vomeronasal olfactory systems each express characteristic odorant receptor families that belong to the G-protein-coupled receptor (GPCR) superfamily; these receptor families define the specific receptive fields and the function of each subsystem (Buck and Axel, 1991; Dulac and Axel, 1995; Herrada and Dulac, 1997; Liberles and Buck, 2006; Liberles et al, 2009; Matsunami and Buck, 1997; Riviere et al, 2009; Ryba and Tirindelli, 1997) The identification of these receptor genes (including the odorant receptors [ORs], vomeronasal type 1 receptors, vomeronasal type 2 receptors [V2Rs], formyl peptide receptors, and the trace amine-associated receptors) has revealed a key organizational principle: each mature olfactory sensory neuron (with the exception of those within the basal subdivision of the vomeronasal system) expresses just a single receptor gene of the hundreds encoded in the genome (Dalton and Lomvardas, 2015). Individual basal vomeronasal sensory neurons target specific bulb glomeruli but express two V2Rs instead of a single receptor (Martini et al, 2001)

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