Olfactory receptors in non-chemosensory tissues

Kang, NaNa; Koo, Jae Hyung

doi:10.5483/bmbrep.2012.45.11.232

Cited by 182 publications

(167 citation statements)

References 78 publications

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“…The olfactory receptor family includes about 350 genes and they are usually expressed in the olfactory epithelium. Several kinds of olfactory receptors have been identified in tissues other than olfactory tissues, including the testis, tongue, and placenta; however, functions of most olfactory receptors expressed in nonolfactory tissues are still elusive (28). A previous study showed that an olfactory receptor, OR51E2, is expressed in prostate cancer cells and that activation of OR51E2 by its ligand, b-ionone and inhibited proliferation of prostate cancer cells (29).…”

Section: Discussionmentioning

confidence: 99%

Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer–Initiating Cells and Is a Potent Target of Immunotherapy

Morita

Hirohashi

Torigoe

et al. 2016

Clinical Cancer Research

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Purpose: Cancer-initiating cells (CICs) are thought to be essential for tumor maintenance, recurrence, and distant metastasis, and they are therefore reasonable targets for cancer therapy. Cancer immunotherapy is a novel approach to target cancer. In this study, we aimed to establish novel CIC-targeting immunotherapy.Experimental Design: Colorectal cancer (CRC) CICs were isolated as side population (SP) cells. The gene expression profile of CRC CICs was analyzed by cDNA microarray and RT-PCR. Protein expression of olfactory receptor family 7 subfamily C member 1 (OR7C1) were analyzed by Western blot and immunohistochemical staining. The functions of OR7C1 were analyzed by gene overexpression and gene knockdown using siRNAs. OR7C1-positive cells were isolated by a flow cytometer and analyzed. CTLs specific for OR7C1 peptide were generated, and the antitumor effect was addressed by mice adoptive transfer model.Results: OR7C1 has essential roles in the maintenance of colon CICs, and the OR7C1-positive population showed higher tumorigenicity than that of the OR7C1-negative population, indicating that OR7C1 is a novel functional marker for colon CIC. Immunohistochemical staining revealed that OR7C1 high expression was correlated with poorer prognosis in CRC patients. OR7C1-derived antigenic peptide-specific CTLs showed specific cytotoxicity for CICs, and an OR7C1-specific CTL clone showed a greater antitumor effect than did a CTL clone targeting all cancer cells in a CTL adoptive transfer mouse model.Conclusions: OR7C1 is a novel marker for colon CICs and can be a target of potent CIC-targeting immunotherapy. Clin Cancer Res; 22(13); 3298-309. Ó2016 AACR.

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Section: Discussionmentioning

confidence: 99%

Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer–Initiating Cells and Is a Potent Target of Immunotherapy

Morita

Hirohashi

Torigoe

et al. 2016

Clinical Cancer Research

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“…In some instances, usefulness may follow linkage to the olfactory genome. In turn, various olfactory receptors, in addition to responding to odors in the nose, likely also play assorted roles in various nonolfactory organs and functions (38)(39)(40). Olfactory fingerprints may provide a measure for these receptors, and therefore serve as a predictive tool for their respective nonolfactory functions as well.…”

Section: Discussionmentioning

confidence: 99%

Individual olfactory perception reveals meaningful nonolfactory genetic information

Secundo

Snitz

Weissler

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Each person expresses a potentially unique subset of ∼400 different olfactory receptor subtypes. Given that the receptors we express partially determine the odors we smell, it follows that each person may have a unique nose; to capture this, we devised a sensitive test of olfactory perception we termed the "olfactory fingerprint." Olfactory fingerprints relied on matrices of perceived odorant similarity derived from descriptors applied to the odorants. We initially fingerprinted 89 individuals using 28 odors and 54 descriptors. We found that each person had a unique olfactory fingerprint (P < 10 −10 ), which was odor specific but descriptor independent. We could identify individuals from this pool using randomly selected sets of 7 odors and 11 descriptors alone. Extrapolating from this data, we determined that using 34 odors and 35 descriptors we could individually identify each of the 7 billion people on earth. Olfactory perception, however, fluctuates over time, calling into question our proposed perceptual readout of presumably stable genetic makeup. To test whether fingerprints remain informative despite this temporal fluctuation, building on the linkage between olfactory receptors and HLA, we hypothesized that olfactory perception may relate to HLA. We obtained olfactory fingerprints and HLA typing for 130 individuals, and found that olfactory fingerprint matching using only four odorants was significantly related to HLA matching (P < 10 −4 ), such that olfactory fingerprints can save 32% of HLA tests in a population screen (P < 10 −6 ). In conclusion, a precise measure of olfactory perception reveals meaningful nonolfactory genetic information.olfactory perception | HLA | MHC | olfactory genetics | autoimmunity H umans have superb olfactory discrimination (1, 2), likely reflecting the combined output of ∼400 different subtypes of olfactory receptors (3). Specific olfactory receptors are likely responsible for specific aspects of olfactory perception (4-7). Because any two individuals differ by ∼30% of their olfactory receptor subtype genome (8), this renders a potentially unique nose for each person (4, 9). If we could capture this uniqueness with a perceptual test, a sort of perceptual olfactory fingerprint, this should then be informative on the underlying individual olfactory receptor subtype genome. The notion of a psychophysical test informing on underlying genes is of course well known from vision, where color blindness charts inform us about genes coding for different opsins in the retina (10). In olfaction, specific anosmias can also point to alterations in a specific gene (4,11,12). Unlike in color vision or specific anosmias, the olfactory fingerprints we propose will likely not inform on a specific gene, but they may link overall perception to overall genetic makeup.Moreover, because the olfactory receptor genome is linked to various other genetic loci, this perceptual test may inform on genetic makeup beyond olfaction alone. For example, the olfactory receptor subtype genome is linked to MHC ge...

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“…Furthermore, ORs maintain up to 40% genetic similarity with rhodopsin (43). Additionally, ORs appear within areas of mammalian corpus that have no olfactory capacity (44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55). We therefore hypothesize that due to functional and morphological similarities, if ORs are activated through an ET mechanism, other GPCRs share the same fundamental mechanism.…”

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confidence: 99%

Experimental evaluation of the generalized vibrational theory of G protein-coupled receptor activation

Hoehn

Nichols

McCorvy

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Recently, an alternative theory concerning the method by which olfactory proteins are activated has garnered attention. This theory proposes that the activation of olfactory G protein-coupled receptors occurs by an inelastic electron tunneling mechanism that is mediated through the presence of an agonist with an appropriate vibrational state to accept the inelastic portion of the tunneling electron's energy. In a recent series of papers, some suggestive theoretical evidence has been offered that this theory may be applied to nonolfactory G protein- O lfaction-and other chemo-sensitive sensory processes-is an important information-gathering technique for organisms of many clades and kingdoms. Specifically, human olfaction is known to occur by activation of olfactory receptors (ORs)-a subclass of G protein-coupled receptors (GPCRs)-located within the nasal epithelium and mediating responses within the olfactory bulb, where it is encoded and conveys information to the amygdala, the orbitofrontal cortex, and the hippocampus (1, 2). The discovery and the cloning of ORs led to the joint 2004 Nobel Prize in Physiology and Medicine to Richard Axel and Linda Buck. (3) GPCRs are 7-helical transmembrane proteins, facilitating communication from extracellular ligand signals to the cellular interior through activation of (interior) G proteins, while maintaining the integrity of the membrane (4). GPCRs are activated by an appropriate agonist moving into the protein's orthosteric binding site, resulting in a conformational change within the helical bundle. This structural change leads to altered conformations of the intracellular loops that couple to appropriate signaling molecules within the cell, e.g., G proteins. A recent series of papers has experimentally determined activated/inactivated states through isotopic-tagged receptors with NMR spectroscopy (5-7). An additional work used molecular dynamics to provide structural insights into how the agonist may assist the interchange between conformations through several proposed peptide sidechain pathways by examining the structures of the activated and inactivated µ-opioid receptor (8). Additionally, photon-induced conformational changes in lightsensitive proteins have also been observed (9, 10).Recently, an iteration of the vibrational theory of olfaction (VTO)-suggested and advocated by Luca Turin (11, 12)-has arisen and has gained both supporters (13-16) and detractors (17, 18); the novelty of this incarnation of the VTO is ascribable to its nonthermal-and nonphoton-based mechanism. Turin's theory is a contemporary reincarnation of the more classical theory proposed by Dyson (19), Wright (20), and Wright and Serenius (21), where the activation of the olfactory receptor is performed-or sensitive to-the molecular vibrations of the olfactant. Dyson suggested that the molecular vibrations of the agonist were exactly responsible for the activation of the protein. These vibrations were entirely thermally excited, as no mechanism for photoexcitation is available within the body. Th...

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Olfactory receptors in non-chemosensory tissues

Cited by 182 publications

References 78 publications

Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer–Initiating Cells and Is a Potent Target of Immunotherapy

Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer–Initiating Cells and Is a Potent Target of Immunotherapy

Individual olfactory perception reveals meaningful nonolfactory genetic information

Experimental evaluation of the generalized vibrational theory of G protein-coupled receptor activation

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