Deorphanization of Olfactory Trace Amine-Associated Receptors

Olfaction is the primary sense used by most animals to perceive the external world. The mouse olfactory system is composed of several sensory structures, the largest of which is the main olfactory epithelium (MOE). Olfactory sensory neurons (OSNs) located within the MOE detect odors and pheromones using dedicated seven-transmembrane G protein-coupled receptors (GPCRs). Two families of GPCRs are expressed in the MOE and are conserved in humans and other vertebrates: odorant receptors (ORs) and trace amine-associated receptors (TAARs). TAARs are distantly related to biogenic amine receptors, such as dopamine and serotonin receptors. Several TAARs detect volatile amines including ethological odors that evoke innate animal behavioral responses. Mouse TAAR4 recognizes the aversive predator odor 2-phenylethylamine, while mouse TAAR5 detects the attractive male mouse odor trimethylamine. In zebrafish, TAAR13c detects the foul death-associated odor cadaverine that mediates innate avoidance behavior. TAARs thus provide an excellent model subsystem to study odor valence. And identification of additional high-affinity ligands for TAARs will provide extra tools for such study. Therefore, this chapter focuses on the so-called SEAP assay that has been successfully applied for TAAR deorphanization in different species.