Functional Characterization of the Odorant Receptor 51E2 in Human Melanocytes

Gelis, Lian; Jovancevic, Nikolina; Veitinger, Sophie; Mandal, Bhubaneswar; Arndt, Hans‐Dieter; Neuhaus, Eva M.; Hatt, Hanns

doi:10.1074/jbc.m116.734517

Cited by 78 publications

(130 citation statements)

References 72 publications

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“…Interestingly, different oligomerization states can be observed for the same receptor also in other tissues. The OR51E1 paralogous olfactory receptor 51E2 was found as monomer in the prostate and in human pigment cells in a monomeric and dimeric form [33, 67]. …”

Section: Discussionmentioning

confidence: 99%

Medium-chain fatty acids modulate myocardial function via a cardiac odorant receptor

et al. 2017

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Several studies have demonstrated the expression of odorant receptors (OR) in various human tissues and their involvement in different physiological and pathophysiological processes. However, the functional role of ORs in the human heart is still unclear. Here, we firstly report the functional characterization of an OR in the human heart. Initial next-generation sequencing analysis revealed the OR expression pattern in the adult and fetal human heart and identified the fatty acid-sensing OR51E1 as the most highly expressed OR in both cardiac development stages. An extensive characterization of the OR51E1 ligand profile by luciferase reporter gene activation assay identified 2-ethylhexanoic acid as a receptor antagonist and various structurally related fatty acids as novel OR51E1 ligands, some of which were detected at receptor-activating concentrations in plasma and epicardial adipose tissue. Functional investigation of the endogenous receptor was carried out by Ca2+ imaging of human stem cell-derived cardiomyocytes. Application of OR51E1 ligands induced negative chronotropic effects that depended on activation of the OR. OR51E1 activation also provoked a negative inotropic action in cardiac trabeculae and slice preparations of human explanted ventricles. These findings indicate that OR51E1 may play a role as metabolic regulator of cardiac function.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-017-0600-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Medium-chain fatty acids modulate myocardial function via a cardiac odorant receptor

et al. 2017

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“…This study first uncovered the presence of an OR in the nuclear envelope. To date, the presence of an OR beyond the cytoplasmic membrane was only described for OR2A4, which is localized to the cytokinetic structures of HeLa cells, and for other ORs in the sperm, melanocytes, and brain (Zhang et al, 2012; Flegel et al, 2016; Gelis et al, 2016; Garcia-Esparcia et al, 2013). …”

Section: Discussionmentioning

confidence: 99%

“…OR2AT4 is another example of the therapeutic potential of ORs in human skin because its activation promotes wound healing processes in human keratinocytes (Busse et al, 2014). They are also of major importance for the regulation of apoptosis, cytokinesis, hormone secretion and differentiation (Braun et al, 2007; Zhang et al, 2012; Maßberg et al, 2015; Gelis et al, 2016; Manteniotis et al, 2016a,b; Massberg et al, 2016; Tsai et al, 2016). However, the expression and localization of ORs in different areas of the brain, the spinal cord, the trigeminal (TG) and dorsal root ganglia (DRG) were recently described (Otaki et al, 2004; Garcia-Esparcia et al, 2013; Flegel et al, 2015; Goncalves et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Deep Sequencing of the Human Retinae Reveals the Expression of Odorant Receptors

Jovancevic

Wunderlich

Haering

et al. 2017

Front. Cell. Neurosci.

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Several studies have demonstrated that the expression of odorant receptors (ORs) occurs in various tissues. These findings have served as a basis for functional studies that demonstrate the potential of ORs as drug targets for a clinical application. To the best of our knowledge, this report describes the first evaluation of the mRNA expression of ORs and the localization of OR proteins in the human retina that set a stage for subsequent functional analyses. RNA-Sequencing datasets of three individual neural retinae were generated using Next-generation sequencing and were compared to previously published but reanalyzed datasets of the peripheral and the macular human retina and to reference tissues. The protein localization of several ORs was investigated by immunohistochemistry. The transcriptome analyses detected an average of 14 OR transcripts in the neural retina, of which OR6B3 is one of the most highly expressed ORs. Immunohistochemical stainings of retina sections localized OR2W3 to the photosensitive outer segment membranes of cones, whereas OR6B3 was found in various cell types. OR5P3 and OR10AD1 were detected at the base of the photoreceptor connecting cilium, and OR10AD1 was also localized to the nuclear envelope of all of the nuclei of the retina. The cell type-specific expression of the ORs in the retina suggests that there are unique biological functions for those receptors.

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“…Similarly, it was found that Olfr78 (the murine ortholog) responded to acetate and propionate, but not β-ionone(3). However, a study in 2016 did show evidence that β ionone is a functional ligand: this study demonstrated that cells natively expressing OR51E2 exhibited an increase in intracellular calcium in response to β ionone which was negated by transfection of siRNA for OR51E2 (27). In late 2015, it was reported that Olfr78 responded to lactate in addition to acetate and propionate(28), and this was confirmed by two other groups in 2016 (29, 30).…”

Section: Short Chain Fatty Acid Receptorsmentioning

confidence: 96%

Microbial Short-Chain Fatty Acids and Blood Pressure Regulation

2017

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Purpose of Review Microbial short chain fatty acids (SCFAs) are byproducts of microbial metabolism which can be absorbed into the bloodstream of the host, where they exert effects on host physiology. SCFAs have been known to influence several aspects of host physiology, including the regulation of blood pressure. In this review, we will consider recent studies linking SCFAs to blood pressure regulation. Recent findings Several recent studies have found that changes in blood pressure often coordinate with expected changes in SCFAS. Efforts are now well underway to dissect and better understand this potential connection. One way that SCFAs can influence host cells is by interacting with host GPCRs, including Gpr41 and Olfr78, among others. Intriguingly, mice null for Olfr78 are hypotensive, whereas mice null for Gpr41 are hypertensive, implying that these pathways may be physiologically important links between SCFAs and host blood pressure control. Summary In sum, these studies demonstrate that there does indeed appear to be a link between SCFAs and blood pressure, which likely involves host GPCRs, at least in part – however, the details and intricacies of these interactions are not yet fully understood, and will greatly benefit from further studies.

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Functional Characterization of the Odorant Receptor 51E2 in Human Melanocytes

Cited by 78 publications

References 72 publications

Medium-chain fatty acids modulate myocardial function via a cardiac odorant receptor

Medium-chain fatty acids modulate myocardial function via a cardiac odorant receptor

Deep Sequencing of the Human Retinae Reveals the Expression of Odorant Receptors

Microbial Short-Chain Fatty Acids and Blood Pressure Regulation

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