Characterization of the Olfactory Receptors Expressed in Human Spermatozoa

Flegel, Caroline; Vogel, Felix C. E.; Hofreuter, Adrian; Schreiner, Benjamin S. P.; Osthold, Sandra; Veitinger, Sophie; Becker, Christian; Brockmeyer, Norbert H.; Muschol, Michael; Wennemuth, Gunther; Altmüller, Janine; Hatt, Hanns; Gisselmann, Günter

doi:10.3389/fmolb.2015.00073

Cited by 77 publications

(108 citation statements)

References 57 publications

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“…Eight of the ORs (OR6B3, OR10AD1, OR13J1, OR2L13, OR5P3, OR2H2, OR2L2, and OR2A4/7) were constantly expressed in all of the three for this study generated retina datasets. Our results indicate a conserved OR expression pattern in the human retina as has been described for the olfactory epithelium, the TR/DRG and the spermatozoa/testis of humans (Fuessel et al, 2006; Flegel et al, 2015, 2016). The expression profile of ORs in retina and TG/DRG are very similar.…”

Section: Discussionsupporting

confidence: 80%

“…The detection of annotated 5′UTRs and the corresponding exon-spanning reads is strong evidence for the presence of the OR-transcript. Furthermore, the visualization of OR1Q1 revealed splicing events within their ORF, which are a typical feature of many of the OR-transcripts (Flegel et al, 2016). …”

Section: Resultsmentioning

confidence: 99%

“…This is consistent with the high concentration of cones in the mRetina. OR2W3 is a broadly expressed OR and in some cases it was only found as a chimeric transcript with the E3 ubiquitin-protein ligase TRIM58 , of unknown function (Flegel et al, 2013, 2016). However, in the data newly generated for this study, we observe only chimeric transcripts with TRIM58 in one data set.…”

Section: Discussionmentioning

confidence: 99%

“…The polyclonal rabbit antibodies against OR2W3, OR5P3, and OR10AD1 were obtained from Sigma-Aldrich (St. Louis, MO, USA; HPA045594, HPA060787, HPA049913). The specificity of OR antibodies was verified using recombinantly expressed rho-tagged ORs in Hana3A cells (Supplementary Figure S2; Flegel et al, 2016). As markers for cell compartments following antibodies were applied: monoclonal mouse antibodies against centrin-3 as a marker for the connecting cilium and basal body complex of photoreceptor cells (Trojan et al, 2008) and antibodies against β-catenin (Santa Cruz, Heidelberg, Germany), for the Cis-Golgi GM130 (BD Transduction Laboratories, Heidelberg, Germany), calnexin (Abcam, Cambridge, UK), LAMP1 (Lysosomal-Associated Membrane Protein 1; BD Transduction Laboratories, Heidelberg, Germany), as a markers for the cell adhesions complexes of the outer limiting membrane (OLM), the Cis-Golgi, the ER, and lysosomes, respectively.…”

Section: Methodsmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 80%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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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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“…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.…”

mentioning

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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The Biology of Fertilization

Carroll¹

2018

Clinical Reproductive Science

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Characterization of the Olfactory Receptors Expressed in Human Spermatozoa

Cited by 77 publications

References 57 publications

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

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

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

The Biology of Fertilization

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