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Updated: Jun 20, 2026
Assaying Surface Expression of Chemosensory Receptors in Heterologous Cells
Published on: February 23, 2011
Trafficking of mammalian chemosensory receptors by receptor-transporting proteins
Hiroaki Matsunami1, Joel D Mainland, Sandeepa Dey
1Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Abstract:
Although mammalian odorant receptors (ORs) were identified more than 15 years ago, we still do not understand how odorant molecules interact with ORs at a molecular level. Previous studies of mammalian ORs have tested few ORs against many odorants. Some fundamental properties of the olfactory system, however, require investigation of a wide panel of diverse ORs with many chemically diverse odorants. Previously, we identified OR accessory proteins, receptor-transporting protein (RTP) 1 and RTP2. They are expressed specifically in olfactory neurons, are associated with OR proteins, and facilitate the OR trafficking to the plasma membrane when coexpressed in mammalian cell lines. With this approach, high-throughput screening using a large repertoire of mammalian ORs is now possible. The activation profiles can be used to develop a predictive model relating physicochemical odorant properties, receptor sequences, and their interactions, enabling us to predict a tested receptor's response to a novel odorant and a novel receptor's response to a tested odorant. Doing so will provide a basis for understanding how structurally diverse odorant molecules activate the mammalian OR repertoire. Similarly, two families of vomeronasal receptors, V1Rs and V2Rs, are also notoriously difficult to functionally express in heterologous cells. However, coexpression of the RTP family members with V1Rs or V2Rs does not seem to facilitate trafficking of the receptor proteins. This finding suggests that the vomeronasal organ has a unique biosynthetic pathway for membrane proteins.
Insights
Receptor-transporting proteins (RTPs) facilitate mammalian odorant receptor (OR) trafficking, enabling high-throughput screening. This research provides a basis for predicting odorant-receptor interactions and understanding olfactory system function.
Area of Science:
- Olfactory system research
- Molecular biology
- Neuroscience
Background:
- Mammalian odorant receptors (ORs) were identified over 15 years ago, but their molecular-level interactions with odorants remain poorly understood.
- Previous studies have limited the scope of OR-odorant interaction analysis by testing few receptors against many odorants.
- Understanding fundamental olfactory system properties necessitates investigating a wide range of diverse ORs with chemically varied odorants.
Purpose of the Study:
- To investigate the role of receptor-transporting proteins (RTPs) 1 and 2 in facilitating OR trafficking.
- To enable high-throughput screening of mammalian ORs using a large repertoire.
- To develop a predictive model for odorant-receptor interactions based on physicochemical properties and receptor sequences.
Main Methods:
- Identification and characterization of OR accessory proteins, RTP 1 and RTP 2.
- Coexpression of RTPs with ORs in mammalian cell lines to assess receptor trafficking.
- High-throughput screening of a large repertoire of mammalian ORs.
- Analysis of OR activation profiles to correlate with odorant properties and receptor sequences.
Main Results:
- RTP 1 and RTP 2 are specifically expressed in olfactory neurons and associated with OR proteins.
- Coexpression of RTPs with ORs facilitates OR trafficking to the plasma membrane in mammalian cell lines.
- This approach enables high-throughput screening of a large OR repertoire.
- Coexpression of RTPs with vomeronasal receptors (V1Rs and V2Rs) did not facilitate their trafficking, suggesting a unique vomeronasal organ pathway.
Conclusions:
- RTPs are crucial for the functional expression and trafficking of mammalian ORs.
- The developed high-throughput screening method allows for predictive modeling of odorant-receptor interactions.
- These findings provide a foundation for understanding how diverse odorant molecules activate the mammalian OR repertoire.
- The vomeronasal organ appears to possess a distinct biosynthetic pathway for its membrane proteins.
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