Cell-Based System for Identification of Olfactory Receptors - Bioelectronic Nose: Integration of Biotechnology and Nanotechnology - page 81

Chapter 5
Cell-Based System for Identification
of Olfactory Receptors

Peter Yi Dong, Naihua Natalie Gong and Hiroaki Matsunami

Abstract The discovery and characterization of odorant receptors (ORs) beginning
in the early 1990s have opened up the ability to study olfaction from a molecular
perspective. Hundreds of OR genes that differ between organisms exist, and each
gene codes for a G protein coupled receptor (GPCR) that can be activated by a large
variety of odorants. Thus, the process of deorphaning, or identifying the cognate
ligand(s) for each receptor, is critical for understanding how smells are perceived.
This chapter reviews the usage of heterologous systems and associated accessory
proteins for expressing ORs in vitro, notably the luciferase assay system for high-
throughput OR screening. This in vitro method of characterizing ORs is also
compared to ex vivo preparations, with a discussion of advantages and drawbacks
of each supported by experimental evidence.

5.1 Introduction

The modern age of olfaction research began in 1991 with the discovery of a family of
genes encoding odorant receptors (ORs), which are localized in the cilia of olfactory
sensory neurons (OSNs) found in the olfactory epithelium [ 1 ]. These OSNs adhere to
the “one gene-one neuron” paradigm in that only one type of OR is expressed in each
OSN [ 2 - 4 ]. Mammals have up to 1,500 OR genes, and within this class, mice have
about 1,200 OR-encoding genes while humans have about 400 [ 5 - 8 ]. ORs are G protein
coupled receptors that consist of seven hydrophobic transmembrane domains. They fea-
ture both conserved amino acid sequences that serve as consensus regions that provide
receptor family identity as well as unique residues which impart each type of receptor