Olfactory receptors in non-chemosensory tissues

Abstract

Olfactory receptors (ORs) detect volatile chemicals that lead to the initial perception of smell in the brain. The olfactory receptor (OR) is the first protein that recognizes odorants in the olfactory signal pathway and it is present in over 1,000 genes in mice. It is also the largest member of the G protein-coupled receptors (GPCRs). Most ORs are extensively expressed in the nasal olfactory epithelium where they perform the appropriate physiological functions that fit their location. However, recent whole-genome sequencing shows that ORs have been found outside of the olfactory system, suggesting that ORs may play an important role in the ectopic expression of non-chemosensory tissues. The ectopic expressions of ORs and their physiological functions have attracted more attention recently since MOR23 and testicular hOR17-4 have been found to be involved in skeletal muscle development, regeneration, and human sperm chemotaxis, respectively. When identifying additional expression profiles and functions of ORs in non-olfactory tissues, there are limitations posed by the small number of antibodies available for similar OR genes. This review presents the results of a research series that identifies ectopic expressions and functions of ORs in non-chemosensory tissues to provide insight into future research directions.

Fig. 1.. A schematic diagram of olfactory signal transduction. Olfactory signal transduction begins with the activation of an olfactory receptor (OR) in the ciliary membrane; this leads to an increase in cyclic AMP (cAMP) synthesis through the activation of adenylate cyclase type III (ACIII) via a G protein (G_olf)-coupled cascade. The increase in cAMP concentration causes cyclic nucleotide-gated (CNG) channels to open, leading to an increase in intracellular Ca²⁺ concentration and depolarization of the cell membrane by the Ca²⁺-activated Clchannel. Among several molecules of the olfactory signal transduction, OR, olfactory marker protein (OMP), G_olf protein α-subunit (Gα_olf), and ACIII have known to be olfactory specific molecules.