Olfactory receptor 2 in vascular macrophages drives atherosclerosis by NLRP3-dependent IL-1 production

Science ◽  
2022 ◽  
Vol 375 (6577) ◽  
pp. 214-221
Author(s):  
Marco Orecchioni ◽  
Kouji Kobiyama ◽  
Holger Winkels ◽  
Yanal Ghosheh ◽  
Sara McArdle ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Olfactory Receptor ◽  
Olfactory Receptors ◽  
Atherosclerotic Plaques ◽  
Biological Functions

Sniffing out atherosclerosis Olfactory receptors are best known for their presence in the nose and their role in detecting smells, but they are also present in other tissues and perform additional biological functions. For example, vascular macrophages involved in the pathogenesis of atherosclerosis express multiple subtypes of olfactory receptors. Orecchioni et al . focused on olfactory receptor 2, a receptor for the compound octanal, and identified its contribution to atherosclerosis pathogenesis and the formation of atherosclerotic plaques (see the Perspective by Rayner and Rasheed). The authors show that most of the octanal was not directly derived from the diet, but rather was generated as a by-product of lipid peroxidation, suggesting a potential pathway for intervention. —YN

scholarly journals Molecular Modelling of Oligomeric States of DmOR83b, an Olfactory Receptor in D. Melanogaster

2012 ◽  
Vol 6 ◽  
pp. BBI.S8990 ◽  
Author(s):  
K. Harini ◽  
R. Sowdhamini
Keyword(s):  
Olfactory Receptor ◽  
Olfactory Receptors ◽  
Insect Species ◽  
Agricultural Pests ◽  
Negative Effects ◽  
C Terminus ◽  
Receptor Neurons ◽  
Medical Importance ◽  
G Protein Coupled ◽  
Made In

After the discovery of the complete repertoire of D. melanogaster Olfactory Receptors (ORs), candidate ORs have been identified from at least 12 insect species from four orders (Coleoptera, Lepidoptera, Diptera, and Hymenoptera), including species of economic or medical importance. Although all ORs share the same G-protein coupled receptor structure with seven transmembrane domains, they share poor sequence identity within and between species, and have been identified mainly through genomic data analyses. To date, D. melanogaster remains the only insect species where ORs have been extensively studied, from expression pattern establishment to functional investigations. These studies have confirmed several observations made in vertebrates: one OR type is selectively expressed in a subtype of olfactory receptor neurons, and one olfactory neuron expresses only one type of OR. The olfactory mechanism, further, appears to be conserved between insects and vertebrates. Understanding the function of insect ORs will greatly contribute to the understanding of insect chemical communication mechanisms, particularly with agricultural pests and disease vectors, and could result in future strategies to reduce their negative effects. In this study, we propose molecular models for insect olfactory receptor co-receptor OR83b and its possible functional oligomeric states. The functional similarity of OR83b to GPCRs and ion channels has been exploited for understanding the structure of OR83b. We could observe that C-terminal region (TM4-7) of OR83b is involved in homodimer amd heterodimer formation (with OR22a) which suggests why C-terminus of insect ORs are highly conserved across different species. We also propose two possible ion channel pathways in OR83b: one formed by TM4-5 region with intracellular pore-forming domain and the other formed by TM5-6 with extracellular pore forming domain using analysis of the electrostatics distribution of the pore forming domain.

scholarly journals Organization and distribution of glomeruli in the bowhead whale olfactory bulb

2014 ◽  
Author(s):  
Takushi Kishida ◽  
J. G. M. Thewissen ◽  
Sharon Usip ◽  
John C George ◽  
Robert S Suydam
Keyword(s):  
Olfactory Bulb ◽  
Olfactory Receptor ◽  
Olfactory Receptors ◽  
Molecular Data ◽  
Dorsal Side ◽  
Bowhead Whale ◽  
Model Organisms ◽  
Marker Genes ◽  
Baleen Whales ◽  
Olfactory Receptor Genes

Although modern baleen whales still possess a functional olfactory systems that includes olfactory bulbs, cranial nerve I and olfactory receptor genes, their olfactory capabilities have been reduced profoundly. This is probably in response to their fully aquatic lifestyle. The glomeruli that occur in the olfactory bulb can be divided into two non-overlapping domains, a dorsal domain and a ventral domain. Recent molecular studies revealed that all modern whales have lost olfactory receptor genes and marker genes that are specific to the dorsal domain, and that a modern baleen whale possess only 60 olfactory receptor genes. Here we show that olfactory bulb of bowhead whales (Balaena mysticetus, Mysticeti) lacks glomeruli on the dorsal side, consistent with the molecular data. In addition, we estimate that there are more than 4,000 glomeruli in the bowhead whale olfactory bulb. Olfactory sensory neurons that express the same olfactory receptor in mice generally project to two specific glomeruli in an olfactory bulb, meaning that ratio of the number of olfactory receptors : the number of glomeruli is approximately 1:2. However, we show here that this ratio is not applicable to whales, indicating the limitation of mice as model organisms for understanding the initial coding of odor information among mammals.

scholarly journals Olfactory receptors are displayed on dog mature sperm cells.

1993 ◽  
Vol 123 (6) ◽  
pp. 1441-1452 ◽  
Author(s):  
P Vanderhaeghen ◽  
S Schurmans ◽  
G Vassart ◽  
M Parmentier
Keyword(s):  
Olfactory Receptor ◽  
Germ Line ◽  
Receptor Gene ◽  
Olfactory Receptors ◽  
Olfactory Mucosa ◽  
Mature Sperm ◽  
Sperm Cells ◽  
Olfactory Receptor Gene ◽  
Mammalian Sperm ◽  
Expression Site

Olfactory receptors constitute a huge family of structurally related G protein-coupled receptors, with up to a thousand members expected. We have shown previously that genes belonging to this family were expressed in the male germ line from both dog and human. The functional significance of this unexpected site of expression was further investigated in the present study. We demonstrate that a few dog genes representative of various subfamilies of olfactory receptors are expressed essentially in testis, with little or no expression in olfactory mucosa. Other randomly selected members of the family show the expected site of expression, restricted to the olfactory system. Antibodies were generated against the deduced amino acid sequence of the most abundantly expressed olfactory receptor gene in dog testis. The purified serum was able to detect the gene product (DTMT receptor) in late round and elongated spermatids, as well as in the cytoplasmic droplet that characterizes the maturation of dog sperm cells, and on the tail midpiece of mature spermatozoa. Western blotting further confirmed the presence of a 40-kD immunoreactive protein in the membrane of mature sperm cells. Altogether , these results demonstrate that the main expression site of a subset of the large olfactory receptor gene family is not olfactory mucosa but testis. This expression correlates with the presence of the corresponding protein during sperm cell maturation, and on mature sperm cells. The pattern of expression is consistent with a role as sensor for unidentified chemicals possibly involved in the control of mammalian sperm maturation, migration, and/or fertilization.

scholarly journals Electrophysiological evidence for acidic, basic, and neutral amino acid olfactory receptor sites in the catfish.

1984 ◽  
Vol 84 (3) ◽  
pp. 403-422 ◽  
Author(s):  
J Caprio ◽  
R P Byrd
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Ictalurus Punctatus ◽  
Olfactory Receptor ◽  
Olfactory Receptors ◽  
Receptor Potential ◽  
Side Chains ◽  
Short Side ◽  
Neutral Amino Acids ◽  
Receptor Sites

Electrophysiological experiments indicate that olfactory receptors of the channel catfish, Ictalurus punctatus, contain different receptor sites for the acidic (A), basic (B), and neutral amino acids; further, at least two partially interacting neutral sites exist, one for the hydrophilic neutral amino acids containing short side chains (SCN), and the second for the hydrophobic amino acids containing long side chains (LCN). The extent of cross-adaptation was determined by comparing the electro-olfactogram (EOG) responses to 20 "test" amino acids during continuous bathing of the olfactory mucosa with water only (control) to those during each of the eight "adapting" amino acid regimes. Both the adapting and test amino acids were adjusted in concentrations to provide approximately equal response magnitudes in the unadapted state. Under all eight adapting regimes, the test EOG responses were reduced from those obtained in the unadapted state, but substantial quantitative differences resulted, depending upon the molecular structure of the adapting stimulus. Analyses of the patterns of EOG responses to the test stimuli identified and characterized the respective "transduction processes," a term used to describe membrane events initiated by a particular subset of amino acid stimuli that are intricately linked to the origin of the olfactory receptor potential. Only when the stimulus compounds interact with different transduction processes are the stimuli assumed to bind to different membrane "sites." Four relatively independent L-alpha-amino acid transduction processes (and thus at least four binding sites) identified in this report include: (a) the A process for aspartic and glutamic acids; (b) the B process for arginine and lysine; (c) the SCN process for glycine, alanine, serine, glutamine, and possibly cysteine; (d) the LCN process for methionine, ethionine, valine, norvaline, leucine, norleucine, glutamic acid-gamma-methyl ester, histidine, phenylalanine, and also possibly cysteine. The specificities of these olfactory transduction processes in the catfish are similar to those for the biochemically determined receptor sites for amino acids in other species of fishes and to amino acid transport specificities in tissues of a variety of organisms.

scholarly journals Classes and Narrowing Selectivity of Olfactory Receptor Neurons of Xenopus laevis Tadpoles

2004 ◽  
Vol 123 (2) ◽  
pp. 99-107 ◽  
Author(s):  
Ivan Manzini ◽  
Detlev Schild
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Xenopus Laevis ◽  
Olfactory Receptor ◽  
Developmental Stages ◽  
Olfactory Receptors ◽  
Response Spectra ◽  
Olfactory Receptor Neurons ◽  
Receptor Neurons ◽  
Response Profiles

In olfactory receptor neurons (ORNs) of aquatic animals amino acids have been shown to be potent stimuli. Here we report on calcium imaging experiments in slices of the olfactory mucosa of Xenopus laevis tadpoles. We were able to determine the response profiles of 283 ORNs to 19 amino acids, where one profile comprises the responses of one ORN to 19 amino acids. 204 out of the 283 response profiles differed from each other. 36 response spectra occurred more than once, i.e., there were 36 classes of ORNs identically responding to the 19 amino acids. The number of ORNs that formed a class ranged from 2 to 13. Shape and duration of amino acid-elicited [Ca2+]i transients showed a high degree of similarity upon repeated stimulation with the same amino acid. Different amino acids, however, in some cases led to clearly distinguishable calcium responses in individual ORNs. Furthermore, ORNs clearly appeared to gain selectivity over time, i.e., ORNs of later developmental stages responded to less amino acids than ORNs of earlier stages. We discuss the narrowing of ORN selectivity over stages in the context of expression of olfactory receptors.

scholarly journals Primacy model and the evolution of the olfactory receptor repertoire

2018 ◽  
Author(s):  
Hamza Giaffar ◽  
Dmitry Rinberg ◽  
Alexei A. Koulakov
Keyword(s):  
Olfactory Receptor ◽  
Olfactory Receptors ◽  
Dimensional Structure ◽  
Sufficient Information ◽  
High Affinity ◽  
Receptor Repertoire ◽  
Wide Range ◽  
Evoked Activity ◽  
Low Dimensional ◽  
The Impact

For many animals, the neural activity in early olfactory circuits during a single sniff cycle contains sufficient information for fine odor discrimination. Whilst much is known about the transformations of neural representations in early olfactory circuits, exactly how odorant evoked activity in the main olfactory bulb shapes the perception of odors remains largely unknown. In olfaction, odorant identity is generally conserved over a wide range of conditions, including concentration. We present a theory of identity assignment in the olfactory system that accounts for this invariance with respect to stimulus intensity. We suggest that the identities of relatively few high affinity olfactory receptor types determine an odorant's perceived identity. This set of high-affinity receptors is defined as the primary set and the coding model based on their responses is called the primacy theory. In this study, we explore the impact that primacy coding may have on the evolution of the ensemble of olfactory receptors. A primacy coding mechanism predicts the arrangement of different receptor types in a low-dimensional structure that we call a primacy hull. We present several statistical analyses that can detect the presence of this structure, allowing the predictions of the primacy model to be tested experimentally.

scholarly journals Adaptation of olfactory receptor abundances for efficient coding

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Tiberiu Teşileanu ◽  
Simona Cocco ◽  
Rémi Monasson ◽  
Vijay Balasubramanian
Keyword(s):  
Sensory Neurons ◽  
Olfactory Receptor ◽  
Environmental Changes ◽  
Olfactory Receptors ◽  
Olfactory Sensory Neurons ◽  
Birth And Death Processes ◽  
Global Context ◽  
Efficient Coding ◽  
Receptor Usage ◽  
Striking Fact

Olfactory receptor usage is highly heterogeneous, with some receptor types being orders of magnitude more abundant than others. We propose an explanation for this striking fact: the receptor distribution is tuned to maximally represent information about the olfactory environment in a regime of efficient coding that is sensitive to the global context of correlated sensor responses. This model predicts that in mammals, where olfactory sensory neurons are replaced regularly, receptor abundances should continuously adapt to odor statistics. Experimentally, increased exposure to odorants leads variously, but reproducibly, to increased, decreased, or unchanged abundances of different activated receptors. We demonstrate that this diversity of effects is required for efficient coding when sensors are broadly correlated, and provide an algorithm for predicting which olfactory receptors should increase or decrease in abundance following specific environmental changes. Finally, we give simple dynamical rules for neural birth and death processes that might underlie this adaptation.

scholarly journals Massive Loss of Olfactory Receptors But Not Trace Amine-Associated Receptors in the World’s Deepest-Living Fish (Pseudoliparis swirei)

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 910
Author(s):  
Haifeng Jiang ◽  
Kang Du ◽  
Xiaoni Gan ◽  
Liandong Yang ◽  
Shunping He
Keyword(s):  
Olfactory Receptor ◽  
Olfactory Receptors ◽  
Gene Families ◽  
Evolutionary Divergence ◽  
Ecological Adaptations ◽  
Receptor Repertoire ◽  
Trace Amine ◽  
Feeding Habitat ◽  
Or Genes ◽  
Pressure Analysis

Olfactory receptor repertoires show highly dynamic evolution associated with ecological adaptations in different species. The Mariana snailfish (Pseudoliparis swirei) living below a depth of 6000 m in the Mariana Trench evolved degraded vision and occupies a specific feeding habitat in a dark, low-food environment. However, whether such adaptations involve adaptive changes in the chemosensory receptor repertoire is not known. Here, we conducted a comparative analysis of the olfactory receptor (OR) and trace amine-associated receptor (TAAR) gene repertoires in nine teleosts with a focus on the evolutionary divergence between the Mariana snailfish and its shallow-sea relative, Tanaka’s snailfish (Liparis tanakae). We found many fewer functional OR genes and a significantly higher fraction of pseudogenes in the Mariana snailfish, but the numbers of functional TAAR genes in the two species were comparable. Phylogenetic analysis showed that the expansion patterns of the gene families were shared by the two species, but that Mariana snailfish underwent massive gene losses in its OR repertoire. Despite an overall decreased size in OR subfamilies and a reduced number of TAAR subfamilies in the Mariana snailfish, expansion of certain subfamilies was observed. Selective pressure analysis indicated greatly relaxed selective strength in ORs but a slightly enhanced selective strength in TAARs of Mariana snailfish. Overall, our study reveals simplified but specific OR and TAAR repertoires in the Mariana snailfish shaped by natural selection with respect to ecological adaptations in the hadal environment. This is the first study on the chemosensation evolution in vertebrates living in the hadal zone, which could provide new insights into evolutionary adaptation to the hadal environment.

scholarly journals Renal olfactory receptor 1393 contributes to the progression of type 2 diabetes in a diet-induced obesity model

2019 ◽  
Vol 316 (2) ◽  
pp. F372-F381 ◽  
Author(s):  
Blythe D. Shepard ◽  
Hermann Koepsell ◽  
Jennifer L. Pluznick
Keyword(s):  
Type 2 Diabetes ◽  
Proximal Tubule ◽  
High Fat Diet ◽  
Olfactory Receptor ◽  
Early Stage ◽  
Fasting Blood Glucose ◽  
Olfactory Receptors ◽  
High Fat ◽  
Glucose Reabsorption

Olfactory receptors are G protein-coupled receptors that serve to detect odorants in the nose. Additionally, these receptors are expressed in other tissues, where they have functions outside the canonical smell response. Olfactory receptor 1393 (Olfr1393) was recently identified as a novel regulator of Na+-glucose cotransporter 1 (Sglt1) localization in the renal proximal tubule. Glucose reabsorption in the proximal tubule (via Sglt1 and Sglt2) has emerged as an important contributor to the development of diabetes. Inhibition of Sglt2 is accepted as a viable therapeutic treatment option for patients with type 2 diabetes and has been shown to delay development of diabetic kidney disease. We hypothesized that Olfr1393 may contribute to the progression of type 2 diabetes, particularly the development of hyperfiltration, which has been linked to increased Na+ reabsorption in the proximal tubule via the Sglts. To test this hypothesis, Olfr1393 wild-type (WT) and knockout (KO) mice were challenged with a high-fat diet to induce early-stage type 2 diabetes. After 16 wk on the high-fat diet, fasting blood glucose values were increased and glucose tolerance was impaired in the male WT mice. Both of these effects were significantly blunted in the male KO mice. In addition, male and female WT mice developed diabetes-induced hyperfiltration, which was attenuated in the Olfr1393 KO mice and corresponded with a reduction in luminal expression of Sglt2. Collectively, these data indicate that renal Olfr1393 can contribute to the progression of type 2 diabetes, likely as a regulator of Na+-glucose cotransport in the proximal tubule.

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