Olfactory receptors (ORs) in mammals are generally considered to function as chemosensors in the olfactory organs of animals. They are membrane proteins that traverse the cytoplasmic membrane seven times and work generally by coupling to heterotrimeric G protein. The OR is a G protein‒coupled receptor that binds the guanine nucleotide-binding Gαolf subunit and the Gβγ dimer to recognize a wide spectrum of organic compounds in accordance with its cognate ligand. Mammalian ORs were originally identified from the olfactory epithelium of rat. However, it has been recently reported that the expression of ORs is not limited to the olfactory organ. In recent decades, they have been found to be expressed in diverse organs or tissues and even tumors in mammals. In this review, the expression and expected function of olfactory receptors that exist throughout an organism’s system are discussed.
Animal olfactory receptors (ORs) make up a G proteincoupled chemosensory receptor (GPCR) family with 7 transmembrane alpha-helices located in the cytoplasmic membrane of cells. They are known to work by binding heterotrimeric guanine nucleotide-binding proteins (G proteins), composed of the olfactory G
We discuss the physiological functions of ORs and suggest future perspectives for their research.
Since the expression of ORs in mammalian germ cells was reported [
For the first time, prostate-specific G protein-coupled receptors (PSGRs), also known as RA1c, were reported to be expressed in the brain of rat [
After it was demonstrated that RA1c homologs—Olr59 in rat [
The expression of a mouse OR, Olfr110, was detected in the cerebral cortex of wild-type mice for 1 postnatal year, and its mRNA levels did not vary during that period [
Gong
In 1995, Drutel
Recently, OR10J5 was found to be expressed in human aorta, coronary artery, and human umbilical vein endothelial cells [
Chang
General studies on OR expression show that ORs are expressed throughout systems and have diverse functions throughout the body of animals (
In 1992, ectopic expression of OR-like proteins in dog testis was reported after the OR multigene family was originally isolated from rat olfactory epithelium [
Since three transcripts of OR were identified in rat taste organs and reproductive tissues using an RT-PCR strategy [
According to recent reports, ORs are expressed in non-olfactory tissues, including brain, heart, testis, tongue, GI tract, pancreas [
In human primary keratinocytes, OR2AT4 is expressed and induces wound-healing processes by increasing cell proliferation and migration and regeneration of keratinocyte monolayers [
After an OR was found to be overexpressed in human cancerous prostate and identified as a PSGR (OR51E2) [
In the case of ORs other than PSGRs, mRNA overexpression of OR1D2 was confirmed in LNCap prostate carcinoma cells compared with non-prostate-derived cell lines using RT-PCR, confocal laser scanning microscopy, and fluorescence-activated cell sorting [
Recently, a kind of terpene, the major constituent of essential oils, was observed as an effector in cellular proliferation in hepatocarcinoma cells [
Regardless of their discovery history, it would be better to have an extended view of ORs to get objective analysis results. Besides OR expression, its transportation to the cytoplasmic membrane of a cell is indispensable for correct function. Recently, Sharma
In case of the cancer research, some identified ORs could serve as potential therapeutic targets for cancer diagnosis and its therapeutic applications. All biological phenomena, including cancers, are composite networks. Although much research has been done and is ongoing with regard to ORs, the relationship of the results is not clear. However, it has been proven that molecular functions and physiological changes in various parts could be caused by OR ligands in animal system. Therefore, the future task will be to identify at a holistic level the extent to which OR is involved in overall physiological phenomena
To advance the study of the various functions and roles of ORs, the modularity mechanism that acts between the receptor and its wide-ranged ligands should be addressed.
Selected list of olfactory receptors expressed in system-wide tissues
Tissue | Organism | Representative OR(s) | Remarks (methods, DB, ligand) | Reference |
---|---|---|---|---|
Brain | Rat | RA1c (Olr59) | PCR, NB, ISH | [ |
Mouse | MOL2.3 (RA1c, Olfr78) | PCR, |
[ |
|
Mouse | MOL2.3 (Olfr78) | [ |
||
Mouse | M71 (Olfr151), C6 (Olfr49), (OR3) | Cerebral cortex | [ |
|
Mouse | Olfr110 | AD, PSP, CJD, RT-PCR, cerebral cortex | [ |
|
Human | ORs (↓) | Frontal cortex, PD, microarray | [ |
|
Mouse | Olfr287, etc. | mDA cell, RT-PCR, ISH, FANTOM5 | [ |
|
Human | OR51E1, OR52L1 (↓) | DPC, schizophrenia, PCR | [ |
|
Mouse | Olfr544 | RT-PCR, qPCR | [ |
|
Heart-related | Rat | OL1 (Olr1654) | PCR, ISH | [ |
Mouse, rat | PSGR homolog: RA1c (Olfr78, Olr59) | NB | [ |
|
Mouse | MOL2.3 (Olfr78) | [ |
||
Human | ORs | Microarray | [ |
|
Mouse | Olfr78 | RT-PCR, |
[ |
|
Human | OR10J5 | Human aorta, coronary artery, HUVEC | [ |
|
Mouse | Olfr78 | Carotid body, immunostaining | [ |
|
Rat | ORs | Sciatic nerve, dorsal root ganglia | [ |
|
Mouse | Olfr78 | Carotid body, single-cell RNA-Seq | [ |
|
Human | OR51E1, OR2W3, OR51E2, etc. | TRXM analysis, RT-PCR, WB | [ |
|
Mouse | Olfr544 | RT-PCR, qPCR | [ |
|
Testis | Dog | HGMP07J/I (OR10J1), DTMT | PCR, NB | [ |
Dog | DTMT | Antibody | [ |
|
Rat | OL1 (Olr1654) | PCR, ISH | [ |
|
Rat | OR2 | Antibody | [ |
|
Human | OR4N4, OR2W3, OR3A2, OR10J1, etc. | RNA-Seq | [ |
|
Human | OR4S1, OR1I1, OR4C13 | Testicular tissues, MS, WB, CA | [ |
|
Placenta | Rat | ORs | RT-PCR, WB, IH | [ |
Development | Mouse | Olfr603 | Embryonic tissue, IF | [ |
Erythroid | Human | HPFH1OR (OR52A1) | RT-PCR, erythroid (blood), all stages | [ |
Tongue | Rat | ORs | RT-PCR | [ |
Human | ORs | RT-PCR | [ |
|
Human | ORs | RT-PCR | [ |
|
Human, mouse | ORs | RT-PCR, bioinformatics | [ |
|
GI tract | Mouse | PSGR (Olfr78) | NB | [ |
Human | 4 ORs | RT-PCR, IH, amperometry | [ |
|
Human | OR51E1 | Microarray, RT-PCR, IH | [ |
|
Pig | OR51E1 | RT-qPCR, IH | [ |
|
Human, mouse | OR1A1, OR1G1, OR51E1, Olfr43 | RT-qPCR, siRNA | [ |
|
Pancreas | Rat | OL2 (Olr857) | PCR | [ |
Rat | Orl984 (↓) | RT-PCR | [ |
|
Rat | Orls (↓) | Microarray, bioinformatics | [ |
|
Mouse | Olfr544 | IC, IF, RT-PCR, RNA-Seq, WB | [ |
|
Spleen | Rat | OL2 (Olr857) | MIN6 cell line | [ |
Rat | OdRs | Degenerate primers | [ |
|
Human, mouse, rat | rat OR51E2, Olfr78, Olr59 | NB | [ |
|
Liver | Human, mouse, rat | rat OR51E2, Olfr78, Olr59 | Hepatocyte | [ |
Human | OR1A1 | PCR, IB, IH | [ |
|
Human, mouse | OR10J5, Olfr16 | PCR, WB, siRNA | [ |
|
Mouse | Olfr544 | RT-PCR, qPCR | [ |
|
Kidney | Human | ORs | Microarray | [ |
Mouse | Olfr78, Olfr90, Olfr1373, Olfr1392, Olfr1393 | RT-PCR, WB, IH | [ |
|
Mouse | Olfr78 | RT-PCR, |
[ |
|
Human | OR51E1, OR11H7 | RT-PCR, WB, IC, IH | [ |
|
Mouse | Olfr1393 | RT-PCR, IH, IB | [ |
|
Lung | Mouse | MOL2.3 (Olfr78) | [ |
|
Human | OR51E1 | RT-PCR, IH | [ |
|
Human | OR2J3 | NSCLC | [ |
|
Skin | Human | OR2AT4 | Calcium imaging, wound scratch assay | [ |
Human | OR51E2 | RT-PCR, WB, IC | [ |
|
Muscle | Mouse | Olfr16 (MOR23) | RT-PCR, IB | [ |
Mouse | Olfr16 (MOR23) | RT-PCR, IB | [ |
|
Human | OR51E2 | RT-PCR, CRISPR-Cas9, WB | [ |
|
Human | OR51E1, OR11H7 | RT-PCR, WB, IC, IH | [ |
|
Prostate | Human, mouse, rat | OR51E2, Olfr78, Olr59 | NB | [ |
Human | OR51E2 | RT-PCR, IH | [ |
|
Cancers | Human | PSGR (OR51E2) | CaP, RT-PCR | [ |
Human | PSGR | CaP, RT-PCR | [ |
|
Human | PSGR2 (OR51E1) | CaP, RT-PCR, NB | [ |
|
Human | OR51E2 | CaP, RT-PCR, IH | [ |
|
Human | OR1D2 (OR17-4) | CaP, RT-PCR, CLSM, FACS | [ |
|
Human | PSGR | LNCaP, RT-PCR, calcium imaging | [ |
|
Human | PSGR | LNCaP, MS, IB, calcium imaging | [ |
|
Human | OR51E1 | SI-NEC | [ |
|
Human | OR1A2 | Hepatocarcinoma | [ |
|
Human | OR51B5 | Leukemia | [ |
|
Human | OR7C1 | CRC-CIC | [ |
|
Human | OR3A4 | Gastric cancer | [ |
|
Human | OR2AT4 | Myelogenous leukemia | [ |
|
Human | ORs | Leukemia | [ |
|
Human | OR2J3 | NSCLC | [ |
OR, olfactory receptors; NB, northern blotting; ISH,