Deorphanization of Olfactory Trace Amine-Associated Receptors
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Updated: May 11, 2025
Live-cell Measurement of Odorant Receptor Activation Using a Real-time cAMP Assay
Published on: October 2, 2017
Kang-Ying Qian1,2, Yue Hao1,2, Qian Li3,4
1Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Olfaction is the primary sense used by most animals to perceive the external world. The mouse olfactory system is comprised 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 zebra fish, TAAR13c detects the foul death-associated odor cadaverine that mediates innate avoidance behavior. TAARs thus provide an excellent model subsystem to study odor valence. Identification of additional high-affinity ligands for TAARs will provide extra tools for such study. Therefore, this chapter focuses on the so-called SEAP (secreted alkaline phosphatase) assay that has been successfully applied for TAAR deorphanization in different species.
Insights
Trace amine-associated receptors (TAARs) detect odors and influence animal behavior. The secreted alkaline phosphatase (SEAP) assay is a valuable tool for identifying TAAR ligands and understanding odor valence.
Area of Science:
- Neuroscience
- Sensory Biology
- Biochemistry
Background:
- Olfaction is crucial for animals, with the main olfactory epithelium (MOE) housing olfactory sensory neurons (OSNs).
- OSNs utilize G protein-coupled receptors (GPCRs), including odorant receptors (ORs) and trace amine-associated receptors (TAARs), to detect diverse odorants.
- TAARs are linked to biogenic amine receptors and detect volatile amines, mediating innate behavioral responses to ethological odors.
Purpose of the Study:
- To explore TAARs as a model system for studying odor valence and innate behavioral responses.
- To highlight the utility of the secreted alkaline phosphatase (SEAP) assay for TAAR deorphanization.
- To identify additional high-affinity ligands for TAARs to further research odor perception.
Main Methods:
- Utilized the secreted alkaline phosphatase (SEAP) assay for TAAR deorphanization.
- Focused on identifying ligands for specific TAARs, such as mouse TAAR4 and TAAR5, and zebrafish TAAR13c.
- Applied established biochemical and cellular assays to characterize TAAR-ligand interactions.
Main Results:
- Demonstrated that TAARs detect specific volatile amines with ethological significance (e.g., predator and social odors).
- Showcased the successful application of the SEAP assay in identifying TAAR ligands across different species.
- Provided evidence for TAARs' role in mediating innate behavioral responses, such as attraction and aversion.
Conclusions:
- TAARs represent a key chemosensory system involved in processing biologically relevant odors.
- The SEAP assay is an effective method for discovering novel TAAR ligands and functional characterization.
- Further research into TAAR-ligand interactions will enhance our understanding of odor valence and sensory processing.
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