Hanns Hatt
Ruhr-Universität Bochum, Zellphysiologie, Emeritus
BackgroundTherapeutic options for steroid-resistant non-type 2 inflammation in obstructive lung diseases are lacking. Alveolar macrophages are central in the progression of these diseases by releasing proinflammatory cytokines, making... more
BackgroundTherapeutic options for steroid-resistant non-type 2 inflammation in obstructive lung diseases are lacking. Alveolar macrophages are central in the progression of these diseases by releasing proinflammatory cytokines, making them promising targets for new therapeutic approaches. Extra nasal expressed olfactory receptors (ORs) mediate various cellular processes, but clinical data are lacking. This work investigates whether ORs in human primary alveolar macrophages could impact pathophysiological processes and could be considered as therapeutic targets.MethodsHuman primary alveolar macrophages were isolated from bronchoalveolar lavages of 50 patients with pulmonary diseases. The expression of ORs was validated using RT-PCR, immunocytochemical staining, and Western blot. Changes in intracellular calcium levels were analyzed in real-time by calcium imaging. A luminescent assay was used to measure the cAMP concentration after OR stimulation. Cytokine secretion was measured in c...
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Research Interests: Neuroscience, Biology, Calcium, Enzyme Inhibitors, Medicine, and 15 moreCell separation, Calcium Imaging, Female, Animals, Calcium channels, Male, Calcium Signaling, Epithelial cells, Extracellular Space, Arachidonic Acid, Patch Clamp, Intracellular, Linolenic Acid, Medical and Health Sciences, and Cyclooxygenase
Research Interests: Neuroscience, Biology, Calcium, Cell Biology, Medicine, and 15 moreCell line, Calcium Imaging, Humans, Kidney, Female, Animals, Odors, Receptor, Amino Acid Sequence, Oocytes, Adenosine Triphosphate, Molecular Sequence Data, Cell Membrane, Psychology and Cognitive Sciences, and Medical and Health Sciences
Male-specific olfactory receptor neurons, dissociated from developing antennae of the moth Manduca sexta and grown in long-term primary cell culture, can respond to at least one component of the female moth's sex- pheromone blend with... more
Male-specific olfactory receptor neurons, dissociated from developing antennae of the moth Manduca sexta and grown in long-term primary cell culture, can respond to at least one component of the female moth's sex- pheromone blend with the opening of a nonspecific cation channel. This response does not require the coapplication of pheromone-binding protein.
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We analysed the ligand-based activation mechanism of the prostate-specific G-protein coupled receptor (PSGR), which is an olfactory receptor that mediates cellular growth in prostate cancer cells. Furthermore, it is an olfactory receptor... more
We analysed the ligand-based activation mechanism of the prostate-specific G-protein coupled receptor (PSGR), which is an olfactory receptor that mediates cellular growth in prostate cancer cells. Furthermore, it is an olfactory receptor with a known chemically near identic antagonist/agonist pair, α- and β-ionone. Using a combined theoretical and experimental approach, we propose that this receptor is activated by a ligand-induced rearrangement of a protein-internal hydrogen bond network. Surprisingly, this rearrangement is not induced by interaction of the ligand with the network, but by dynamic van der Waals contacts of the ligand with the involved amino acid side chains, altering their conformations and intraprotein connectivity. Ligand recognition in this GPCR is therefore highly stereo selective, but seemingly lacks any ligand recognition via polar contacts. A putative olfactory receptor-based drug design scheme will have to take this unique mode of protein/ligand action into ...
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Olfactory receptors (ORs) are known to be expressed in a variety of human tissues and act on different physiological processes, such as cell migration, proliferation, or secretion and have been found to function as biomarkers for... more
Olfactory receptors (ORs) are known to be expressed in a variety of human tissues and act on different physiological processes, such as cell migration, proliferation, or secretion and have been found to function as biomarkers for carcinoma tissues of prostate, lung, and small intestine. In this study, we analyzed the OR expression profiles of several different carcinoma tissues, with a focus on breast cancer. The expression of OR2B6 was detectable in breast carcinoma tissues; here, transcripts of OR2B6 were detected in 73% of all breast carcinoma cell lines and in over 80% of all of the breast carcinoma tissues analyzed. Interestingly, there was no expression of OR2B6 observed in healthy tissues. Immunohistochemical staining of OR2B6 in breast carcinoma tissues revealed a distinct staining pattern of carcinoma cells. Furthermore, we detected a fusion transcript containing part of the coding exon of OR2B6 as a part of a splice variant of the histone HIST1H2BO transcript. In addition,...
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The ectopic expression of olfactory receptors (ORs) in the human body has been of major interest in the past decade. Several studies have reported the expression of ORs not only in healthy tissues such as heart, sperm or skin cells, but... more
The ectopic expression of olfactory receptors (ORs) in the human body has been of major interest in the past decade. Several studies have reported the expression of ORs not only in healthy tissues such as heart, sperm or skin cells, but also in cancerous tissues of the liver, prostate or intestine. In the present study, we detected the expression of OR51B5 in the chronic myelogenous leukemia (CML) cell line K562 and in white blood cell samples of clinically diagnosed acute myelogenous leukemia (AML) patients by reverse transcription-PCR and immunocytochemical staining. The known OR51B5 ligand isononyl alcohol increased the levels of intracellular Ca2+ in both AML patient blood cells and K562 cells. With calcium imaging experiments, we characterized in greater detail the OR51B5-mediated signaling pathway. Here, we observed an involvement of adenylate cyclase and the downstream L-type and T-type calcium channels. In addition, the activation of OR51B5 leads to an inhibition of cell pro...
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G protein-coupled receptors (GPCRs) transduce external chemical cues into intracellular signals and are involved in a plethora of physiological processes, but knowledge regarding the function of these receptors in spermatozoa is limited.... more
G protein-coupled receptors (GPCRs) transduce external chemical cues into intracellular signals and are involved in a plethora of physiological processes, but knowledge regarding the function of these receptors in spermatozoa is limited. In the present study, we performed RNA-Seq and analyzed the expression of the all GPCRs except olfactory receptors in human spermatozoa. We revealed the expression of up to 223 different GPCR transcripts in human spermatozoa (FPKM > 0.1) and identified GPR18, a newly described cannabinoid receptor, together with GPR137 and GPR135, as one of the three most highly expressed GPCRs. To date, the expression of GPR18 was completely unknown in human spermatozoa. We confirmed GPR18 expression using RT-PCR and immuncytochemistry experiments and localized the GPR18 protein in the midpiece of human spermatozoa. Stimulation of human spermatozoa with the GPR18 ligand N-arachidonoylglycine induced the phosphorylation of 12 protein kinases, some of them are for...
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Functional characterization of membrane channels by patch clamp techniques has revealed great diversity of transmitter or Voltage gated channels in native membranes. Concomitantly recombinant DNA techniques revealed a plethora of genes... more
Functional characterization of membrane channels by patch clamp techniques has revealed great diversity of transmitter or Voltage gated channels in native membranes. Concomitantly recombinant DNA techniques revealed a plethora of genes encoding channel subunits. Thus functional diversity within a particular class of channels may be generated by families of genes encoding homologous channel subunits that assemble in various combinations into functionally distinct channel subtypes. For most channels the subunit composition and stoichiometry of a particular functional subtype is not yet established except for the nicotinic acetylcholine receptor of Torpedo. One way to identify the subunit composition of channels in native membranes is to compare their functional properties with those of channels expressed in a host membrane, following introduction of subunit coding nucleic acids (cRNA or eDNA) into a host cell. In the case of ligand-gated channels, such as channels gated by acetylcholine (AChR channels) or ?-amino butyric acid (GABAR channels) and voltage gated K+ channels mediating delayed or transient outward currents (RCK channels) it has been shown that particular functions of the channel can be attributed to particular channel subunits. Examples are the %,and e-subunits of skeletal muscle AChR channels or the I~and ?.subunits of GABAR channels, which specify channel subtypes with different pharmacological, kinetic and conductance properties. In the case of voltage gated K + channels single RCK subunits specify functionally diverse homomultimeric K+ channels, which mediate transient and delayed K+ currents. However, heteromultimeric channels with novel properties can also assemble from different RCK subunits. The constituent RCK subunits specify sensitivity to K+ channel blockers, gating and conductance properties. A clear correlation between particular channel phenotypes in the native membrane, their subunit composition and gene regulation of the respective mRNAs has been established for the nicotinic AChR channel in skeletal muscle. Here a developmental switch in the expression of the ?. and e-subunit genes causes a change in end-plate channel properties from the fetal type, composed of ctl3~tS-subunits to the adult type subtype composed of al3&-subunits. Northern blot and in situ hybridisation analysis of AChR subunit specific mRNAs in fetal, adult and denervated skeletal muscle indicate that the expression of subunit specific mRNAs is regulated by multiple transcriptional mechanisms. First, in a mechanism which is restricted to the end-plate, subsynaptic nuclei become "imprinted" early during synaptogenesis to express subunit specific mRNAs. The expression then remains independent of nervous or muscular signals. Second, a more generalized mechanism operates on extrasynaptic nuclei and is dependent on the electrical activity of muscle fibres. Each AChR subunit gene is under multiple transcriptional controls each having different importance for each subunit. The functional diversity of channels may allow control of gene expression by multiple transcription mechanisms. A switch in the expression of genes encoding particular subunits can occur in response to external stimuli causing a change in the channel phenotypes. This may be required for longterm adaptive changes in synaptic efficacy and in electrical excitability of neurones during development or differentiation.
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Olfactory transduction is thought to take place in the outer dendritic membrane of insect olfactory receptor neurons. Here we show that the outer dendritic plasma membrane of silkmoth olfactory receptor neurons seems to be exclusively... more
Olfactory transduction is thought to take place in the outer dendritic membrane of insect olfactory receptor neurons. Here we show that the outer dendritic plasma membrane of silkmoth olfactory receptor neurons seems to be exclusively equipped with a specific ion channel activated by low concentrations of the species-specific sex pheromone component. This so-called AC1 channel has a conductance of 56 pS and is nonselectively permeable to cations. The AC1 channel can be activated from the intracellular side by protein kinase C activators such as diacylglycerol and phorbolester and by cGMP but not by Ca2+, inositol 1,4,5-triphosphate, or cAMP. Our results imply that phosphorylation of this ion channel by protein kinase C could be the crucial step in channel opening by sex pheromones.
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The olfactory signal transduction cascade transforms odor information into electrical signals by a cAMP-based amplification mechanism. The mechanisms underlying the very precise temporal and spatial organization of the relevant signaling... more
The olfactory signal transduction cascade transforms odor information into electrical signals by a cAMP-based amplification mechanism. The mechanisms underlying the very precise temporal and spatial organization of the relevant signaling components remains poorly understood. Here, we report that co-immunoprecipitation experiments identified a macromolecular assembly of signal transduction components in mouse olfactory neurons, organized via MUPP1. Disruption of the PDZ signaling complex through an inhibitory peptide strongly impaired odor responses and changed the activation kinetics of olfactory sensory neurons. In addition, our experiments demonstrated that response termination is dependent on PDZ-based scaffolding. These findings provide new insights into the functional organization and regulation of olfactory signal transduction.
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A growing number of proteins originally found in endocytic structures of the plasma membrane appear to be able to traffic into the nucleus, but the cellular function of this translocation remains unclear. We have found that β-arrestin2,... more
A growing number of proteins originally found in endocytic structures of the plasma membrane appear to be able to traffic into the nucleus, but the cellular function of this translocation remains unclear. We have found that β-arrestin2, which typically shows a cytoplasmic localization owing to constitutive nuclear export, appears in the nucleus after stimulation of the G-protein-coupled odorant receptor hOR17-4. In the nucleus, β-arrestin2 was involved in transcriptional regulation as shown by a Gal4-based transactivation assay. Moreover, we discovered that β-arrestin2 and hOR17-4, a receptor known to have a role in sperm-egg communication, colocalize in the midpiece of mature human spermatozoa. Stimulation of hOR17-4 in spermatozoa induced PKA-dependent translocation of β-arrestin2 to the nucleus and nuclear accumulation of phosphorylated MAPKs. Analysis of the interaction partners of β-arrestin2 indicates that odorant receptor signaling in spermatozoa may be important for the regu...
Research Interests: Biology, Transcription Regulation, Cell Biology, Biological Sciences, Cell line, and 14 moreOdorant Receptor, Humans, Regulation of Gene Expression, Male, Human Spermatozoa, Cell nucleus, Spermatozoa, Cytoplasm, Ligands, Nucleus, Plasma Membrane, Aldehydes, Mitogen- Activated Protein Kinases, and Medical and Health Sciences
Research Interests: Biology, Calcium, Cell Biology, Biological Chemistry, Medicine, and 15 moreBiological Sciences, Motility, Cell line, Humans, Male, Biological, Flagella, Chemotaxis, Phenotype, CHEMICAL SCIENCES, Biological Assay, Acrosome Reaction, Nucleotides, Gene Expression Regulation, and Medical and Health Sciences
Research Interests: Biology, Calcium, Prostate Cancer, Biological Chemistry, Cancer Research, and 15 moreMedicine, Cell Division, Biological Sciences, Humans, Kidney, Male, Biological, Prostate, Phosphorylation, CHEMICAL SCIENCES, Receptor, Ligands, Olfactory Epithelium, Prostatic neoplasms, and Medical and Health Sciences
Research Interests: Biology, Enzyme Inhibitors, Cell Biology, Biological Chemistry, Medicine, and 15 moreBiological Sciences, Humans, Swimming speed, Sperm, Male, Flagella, Calcium Signaling, Chemotaxis, Spatial Distribution, CHEMICAL SCIENCES, Adenylate Kinase, Receptor, Sperm Motility, Adenine, and Medical and Health Sciences
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Research Interests: Electrophysiology, Biology, Medicine, Gene expression, Biological Sciences, and 12 moreHumans, Female, Smell, Male, Chemotaxis, Adult, Spermatozoa, Aldehydes, Psychology and Cognitive Sciences, reverse transcriptase polymerase chain reaction, Dual (grammatical number), and Medical and Health Sciences
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Research Interests: Biology, Cell Biology, Chemical, Medicine, Biological Sciences, and 15 moreCell line, Odorant Receptor, Humans, Mice, Animals, Male, Endoplasmic Reticulum, Green Fluorescent Protein, Chemical Senses, Heat Shock Protein, Heterologous Expression, Germ Cell, Gene Expression Regulation, Molecular Sequence Data, and Olfactory Epithelium
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TRPM8 (CMR1) is a Ca2+‐permeable channel, which can be activated by low temperatures, menthol, eucalyptol and icilin. It belongs to the transient receptor potential (TRP) family, and therefore is related to vanilloid receptor type‐1 (VR1,... more
TRPM8 (CMR1) is a Ca2+‐permeable channel, which can be activated by low temperatures, menthol, eucalyptol and icilin. It belongs to the transient receptor potential (TRP) family, and therefore is related to vanilloid receptor type‐1 (VR1, TRPV1). We tested whether substances which are structurally related to menthol, or which produce a cooling sensation, could activate TRPM8, and compared the responses of TRPM8 and VR1 to these ligands. The effects of 70 odorants and menthol‐related substances on recombinant mouse TRPM8 (mTRPM8), expressed in HEK293 cells, were examined using a FLIPR® assay. In all, 10 substances (linalool, geraniol, hydroxycitronellal, WS‐3, WS‐23, FrescolatMGA, FrescolatML, PMD38, CoolactP and Cooling Agent 10) were found to be agonists. The EC50 values of the agonists defined their relative potencies: icilin (0.2±0.1 μM)>FrescolatML (3.3±1.5 μM) > WS‐3 (3.7±1.7 μM) >(−)menthol (4.1±1.3 μM) >frescolatMAG (4.8±1.1 μM) > cooling agent 10 (6±2.2 μM) &g...
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The HschiA1 gene of the archaeon Halobacterium salinarum CECT 395 was cloned and overexpressed as an active protein of 66.5 kDa in Escherichia coli. The protein called HsChiA1p has a modular structure consisting of a glycosyl hydrolase... more
The HschiA1 gene of the archaeon Halobacterium salinarum CECT 395 was cloned and overexpressed as an active protein of 66.5 kDa in Escherichia coli. The protein called HsChiA1p has a modular structure consisting of a glycosyl hydrolase family 18 catalytic region, as well as a N-terminal family 5 carbohydrate-binding module and a polycystic kidney domain. The purified recombinant chitinase displayed optimum catalytic activity at pH 7.3 and 40 °C and showed high stability over broad pH (6-8.5) and temperature (25-45 °C) ranges. Protein activity was stimulated by the metal ions Mg(+2), K(+), and Ca(+2) and strongly inhibited by Mn(+2). HsChiA1p is salt-dependent with its highest activity in the presence of 1.5 M of NaCl, but retains 20% of its activity in the absence of salt. The recombinant enzyme hydrolysed p-NP-(GlcNAc)3, p-NP-(GlcNAc), crystalline chitin, and colloidal chitin. From its sequence features and biochemical properties, it can be identified as an exo-acting enzyme with potential interest regarding the biodegradation of chitin waste or its bioconversion into biologically active products.
Research Interests: Biochemistry, Enzyme Inhibitors, Gene expression, Multidisciplinary, Escherichia coli, and 15 moreTemperature, Metals, Recombinant DNA, Applied Microbiology and Biotechnology, Molecular cloning, Aquatic organisms, Substrate Specificity, Chitinase, Halobacterium Salinarum, Molecular weight, Recombinant Proteins, Hydrogen-Ion Concentration, Chitin, Sodium Chloride, and Ions
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Odorant receptors comprise the biggest subfamily of G-protein-coupled receptors. Although the endocytic mechanisms of other G-protein-coupled receptors have been characterized extensively, almost nothing is known about the intracellular... more
Odorant receptors comprise the biggest subfamily of G-protein-coupled receptors. Although the endocytic mechanisms of other G-protein-coupled receptors have been characterized extensively, almost nothing is known about the intracellular trafficking of odorant receptors. The present study describes the endocytic pathway of mammalian odorant receptors, which bind β-arrestin2 with high affinity and are internalized via a clathrin-dependent mechanism. After prolonged odorant exposure, receptors are not targeted to lysosomal degradation but accumulate in recycling endosomes. Odorant-induced odorant receptor desensitization is promoted by cAMP-dependent protein kinase A phosphorylation and is dependent on serine and threonine residues within the third intracellular loop of the receptor. Moreover, β-arrestin2 is redistributed into the dendritic knobs of mouse olfactory receptor neurons after treatment with a complex odorant mixture. Prolonged odorant exposure resulted in accumulation of β-...
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Olfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer.... more
Olfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment...
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Olfactory receptors (ORs) are not exclusively expressed in the olfactory sensory neurons; they are also observed outside of the olfactory system in all other human tissues tested to date, including the testis, lung, intestine, skin,... more
Olfactory receptors (ORs) are not exclusively expressed in the olfactory sensory neurons; they are also observed outside of the olfactory system in all other human tissues tested to date, including the testis, lung, intestine, skin, heart, and blood. Within these tissues, certain ORs have been determined to be exclusively expressed in only one tissue, whereas other ORs are more widely distributed in many different tissues throughout the human body. For most of the ectopically expressed ORs, limited data are available for their functional roles. They have been shown to be involved in the modulation of cell-cell recognition, migration, proliferation, the apoptotic cycle, exocytosis, and pathfinding processes. Additionally, there is a growing body of evidence that they have the potential to serve as diagnostic and therapeutic tools, as ORs are highly expressed in different cancer tissues. Interestingly, in addition to the canonical signaling pathways activated by ORs in olfactory senso...
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The odorant receptor 51E2 (OR51E2), which is well-characterized in prostate cancer cells and epidermal pigment cells, was identified for the first time as the most highly expressed OR in human fetal and adult retinal pigment epithelial... more
The odorant receptor 51E2 (OR51E2), which is well-characterized in prostate cancer cells and epidermal pigment cells, was identified for the first time as the most highly expressed OR in human fetal and adult retinal pigment epithelial (RPE) cells. Immunofluorescence staining and Western blot analysis revealed OR51E2 localization throughout the cytosol and in the plasma membrane. Additionally, immunohistochemical staining of diverse layers of the eye showed that the expression of OR51E2 is restricted to the pigment cells of the RPE and choroid. The results of Ca-imaging experiments demonstrate that activation of OR51E2 triggers a Cadependent signal pathway in RPE cells. Downstream signaling of OR51E2 involves the activation of adenylyl cyclase, ERK1/2 and AKT. The activity of these protein kinases likely accounts for the demonstrated increase in the migration and proliferation of RPE cells upon stimulation with the OR51E2 ligand β-ionone. These findings suggest that OR51E2 is involv...
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The olfactory receptor (OR) family was found to be expressed mainly in the nasal epithelium. In the last two decades members of the OR family were detected to be functional expressed in different parts of the human body such as in liver,... more
The olfactory receptor (OR) family was found to be expressed mainly in the nasal epithelium. In the last two decades members of the OR family were detected to be functional expressed in different parts of the human body such as in liver, prostate or intestine cancer cells. Here, we detected the expression of several ORs in the human chronic myelogenous leukemia (CML) cell line K562 and in white blood cells of clinically diagnosed acute myeloid leukemia (AML) patients by RT-PCR and next-generation sequencing. With calcium-imaging, we characterized in greater detail the cell biological role of one OR (OR2AT4) in leukemia. In both cell systems, the OR2AT4 agonist Sandalore-evoked strong Ca2+ influx via the adenylate cyclase-cAMP-mediated pathway. The OR2AT4 antagonist Phenirat prevented the Sandalore-induced intracellular Ca2+ increase. Western blot and flow cytometric experiments revealed that stimulation of OR2AT4 reduced the proliferation by decreasing p38-MAPK phosphorylation and i...
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BEACH domain proteins are involved in membrane protein traffic and human diseases, but their molecular mechanisms are not understood. The BEACH protein LRBA has been implicated in immune response and cell proliferation, and human LRBA... more
BEACH domain proteins are involved in membrane protein traffic and human diseases, but their molecular mechanisms are not understood. The BEACH protein LRBA has been implicated in immune response and cell proliferation, and human LRBA mutations cause severe immune deficiency. Here, we report a first functional and molecular phenotype outside the immune system of LRBA-knockout mice: compromised olfaction, manifesting in reduced electro-olfactogram response amplitude, impaired food-finding efficiency, and smaller olfactory bulbs. LRBA is prominently expressed in olfactory and vomeronasal chemosensory neurons of wild-type mice. Olfactory impairment in the LRBA-KO is explained by markedly reduced concentrations (20-40% of wild-type levels) of all three subunits αolf, β1 and γ13 of the olfactory heterotrimeric G-protein, Golf, in the sensory cilia of olfactory neurons. In contrast, cilia morphology and the concentrations of many other proteins of olfactory cilia are not or only slightly ...
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The analysis and functional characterization of ectopically expressed human olfactory receptors (ORs) is becoming increasingly important, as many ORs have been identified in several healthy and cancerous tissues. OR activation has been... more
The analysis and functional characterization of ectopically expressed human olfactory receptors (ORs) is becoming increasingly important, as many ORs have been identified in several healthy and cancerous tissues. OR activation has been demonstrated to have influence on cancer cell growth and progression. Here, ORs were identified using RNA-Seq analyses and RT-PCR. We demonstrated the OR protein localization in HCT116 cells using immunocytochemistry (IHC). In order to analyze the physiological role of OR51B4, we deorphanized the receptor by the use of CRE-Luciferase assays, conducted calcium imaging experiments as well as scratch- and proliferation assays. Furthermore, western blot analyses revealed the involvement of different protein kinases in the ligand-dependent signaling pathway. Receptor knockdown via shRNA was used to analyze the involvement of OR51B4. We identified OR51B4, which is highly expressed in the colon cancer cell line HCT116 and in native human colon cancer tissues...
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The secretion, motility and transport by intestinal tissues are regulated among others by specialized neuroendocrine cells, the so-called enterochromaffin (EC) cells. These cells detect different luminal stimuli, such as mechanical... more
The secretion, motility and transport by intestinal tissues are regulated among others by specialized neuroendocrine cells, the so-called enterochromaffin (EC) cells. These cells detect different luminal stimuli, such as mechanical stimuli, fatty acids, glucose and distinct chemosensory substances. The EC cells react to the changes in their environment through the release of transmitter molecules, most importantly serotonin, to mediate the corresponding physiological response. However, little is known about the molecular targets of the chemical stimuli delivered from consumed food, spices and cosmetics within EC cells. In this study, we evaluated the expression of the olfactory receptor (OR) 2J3 in the human pancreatic EC cell line QGP-1 at the mRNA and protein levels. Using ratiofluorometric Ca2+ imaging experiments, we demonstrated that the OR2J3-specific agonist helional induces a transient dose-dependent decrease in the intracellular Ca2+ levels. This Ca2+ decrease is mediated b...
Research Interests: Chemistry, Calcium, Medicine, Molecular endocrinology, Gene expression, and 13 moreSignal Transduction, Serotonin, Cell line, Humans, Calcium Signaling, Clinical Sciences, Stimulation, Veterinary Sciences, Secretion, Intracellular, Enterochromaffin cell, Odorants, and Paediatrics and reproductive medicine
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Research Interests: Genetics, Biology, Cancer Research, Gene expression, Immunocytochemistry, and 15 moreHuman, Cellular Senescence, Humans, Article, Androgen Receptor Signalling, Biosynthesis, Cancer Cell, Controlled Study, Disease Progression, Androgen Receptor, Cell Proliferation, Enzyme Linked Immunosorbent Assay, Human Cell, Castration resistant prostate cancer, and Human Tissue
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It is generally agreed that in olfactory sensory neurons (OSNs), the binding of odorant molecules to their specific olfactory receptor (OR) triggers a cAMP-dependent signaling cascade, activating cyclic-nucleotide gated (CNG) channels.... more
It is generally agreed that in olfactory sensory neurons (OSNs), the binding of odorant molecules to their specific olfactory receptor (OR) triggers a cAMP-dependent signaling cascade, activating cyclic-nucleotide gated (CNG) channels. However, considerable controversy dating back more than 20 years has surrounded the question of whether alternate signaling plays a role in mammalian olfactory transduction. In this study, we demonstrate a specific alternate signaling pathway in Olfr73-expressing OSNs. Methylisoeugenol (MIEG) and at least one other known weak Olfr73 agonist (Raspberry Ketone) trigger a signaling cascade independent from the canonical pathway, leading to the depolarization of the cell. Interestingly, this pathway is mediated by Gnao activation, leading to Cl(-) efflux; however, the activation of adenylyl cyclase III (ACIII), the recruitment of Ca(2+) from extra-or intracellular stores, and phosphatidylinositol 3-kinase-dependent signaling (PI signaling) are not involve...
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Mammalian odor reception is achieved by highly specialized olfactory sensory neurons (OSNs) located in the nasal cavity. Despite their importance for the daily survival of most mammals, the gene expression and regulatory profiles of these... more
Mammalian odor reception is achieved by highly specialized olfactory sensory neurons (OSNs) located in the nasal cavity. Despite their importance for the daily survival of most mammals, the gene expression and regulatory profiles of these single neurons are poorly understood. Here, we report the isolation of individual GFP-labeled OSNs from Olfr73-GFP mice at different developmental stages followed by Next Generation Sequencing, thereby analyzing the detailed transcriptome for the first time. We characterized the repertoire of olfactory receptors (ORs) and found that in addition to the highly and predominant detectable Olfr73, 20 additional ORs were stably detectable at lower transcript levels in adult mice. Additionally, OSNs collected from mice of earlier developmental stages did not show any stable OR patterns. However, more than one predominant OR per OSN was detectable.
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Research Interests: Biology, Medicine, Signal Transduction, Biological Sciences, Olfaction, and 15 moreCell line, Humans, Mutation, Mice, Retinitis pigmentosa, Animals, Human Molecular Genetics, Epithelial cells, Cilia, Gene Expression Regulation, Gene expression profiling, Extracellular Matrix Proteins, Cadherins, Odorants, and Medical and Health Sciences
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Olfaction is one of the most crucial senses for vertebrates regarding foraging and social behavior. Therefore, it is of particular interest to investigate the sense of smell, its function on a molecular level, the signaling proteins... more
Olfaction is one of the most crucial senses for vertebrates regarding foraging and social behavior. Therefore, it is of particular interest to investigate the sense of smell, its function on a molecular level, the signaling proteins involved in the process and the mechanism of required ion transport. In recent years, the precise role of the ion transporter NKCC1 in olfactory sensory neuron (OSN) chloride accumulation has been a controversial subject. NKCC1 is expressed in OSNs and is involved in chloride accumulation of dissociated neurons, but it had not been shown to play a role in mouse odorant sensation. Here, we present electro-olfactogram recordings (EOG) demonstrating that NKCC1-deficient mice exhibit significant defects in perception of a complex odorant mixture (Henkel100) in both air-phase and submerged approaches. Using next generation sequencing and RT PCR experiments of NKCC1-deficient and wild type mouse transcriptomes, we confirmed the absence of a highly expressed io...