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1.
Mol Biol Evol ; 41(4)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38649162

RESUMO

Chemical senses, including olfaction, pheromones, and taste, are crucial for the survival of most animals. There has long been a debate about whether different types of senses might influence each other. For instance, primates with a strong sense of vision are thought to have weakened olfactory abilities, although the oversimplified trade-off theory is now being questioned. It is uncertain whether such interactions between different chemical senses occur during evolution. To address this question, we examined four receptor gene families related to olfaction, pheromones, and taste: olfactory receptor (OR), vomeronasal receptor type 1 and type 2 (V1R and V2R), and bitter taste receptor (T2R) genes in Hystricomorpha, which is morphologically and ecologically the most diverse group of rodents. We also sequenced and assembled the genome of the grasscutter, Thryonomys swinderianus. By examining 16 available genome assemblies alongside the grasscutter genome, we identified orthologous gene groups among hystricomorph rodents for these gene families to separate the gene gain and loss events in each phylogenetic branch of the Hystricomorpha evolutionary tree. Our analysis revealed that the expansion or contraction of the four gene families occurred synchronously, indicating that when one chemical sense develops or deteriorates, the others follow suit. The results also showed that V1R/V2R genes underwent the fastest evolution, followed by OR genes, and T2R genes were the most evolutionarily stable. This variation likely reflects the difference in ligands of V1R/V2Rs, ORs, and T2Rs: species-specific pheromones, environment-based scents, and toxic substances common to many animals, respectively.


Assuntos
Evolução Molecular , Família Multigênica , Filogenia , Receptores Odorantes , Roedores , Órgão Vomeronasal , Animais , Receptores Acoplados a Proteínas G/genética , Receptores Odorantes/genética , Receptores de Feromônios/genética , Receptores de Feromônios/metabolismo , Roedores/genética , Olfato/genética , Paladar/genética , Órgão Vomeronasal/metabolismo
2.
Proc Natl Acad Sci U S A ; 119(21): e2114966119, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35584113

RESUMO

How the human brain translates olfactory inputs into diverse perceptions, from pleasurable floral smells to sickening smells of decay, is one of the fundamental questions in olfaction. To examine how different aspects of olfactory perception emerge in space and time in the human brain, we performed time-resolved multivariate pattern analysis of scalp-recorded electroencephalogram responses to 10 perceptually diverse odors and associated the resulting decoding accuracies with perception and source activities. Mean decoding accuracies of odors exceeded the chance level 100 ms after odor onset and reached maxima at 350 ms. The result suggests that the neural representations of individual odors were maximally separated at 350 ms. Perceptual representations emerged following the decoding peak: unipolar unpleasantness (neutral to unpleasant) from 300 ms, and pleasantness (neutral to pleasant) and perceptual quality (applicability to verbal descriptors such as "fruity" or "flowery") from 500 ms after odor onset, with all these perceptual representations reaching their maxima after 600 ms. A source estimation showed that the areas representing the odor information, estimated based on the decoding accuracies, were localized in and around the primary and secondary olfactory areas at 100 to 350 ms after odor onset. Odor representations then expanded into larger areas associated with emotional, semantic, and memory processing, with the activities of these later areas being significantly associated with perception. These results suggest that initial odor information coded in the olfactory areas (<350 ms) evolves into their perceptual realizations (300 to >600 ms) through computations in widely distributed cortical regions, with different perceptual aspects having different spatiotemporal dynamics.


Assuntos
Mapeamento Encefálico , Encéfalo , Odorantes , Percepção Olfatória , Encéfalo/fisiologia , Eletroencefalografia , Emoções , Humanos , Memória , Olfato
3.
Hum Brain Mapp ; 45(6): e26681, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38656060

RESUMO

Olfactory perception depends not only on olfactory inputs but also on semantic context. Although multi-voxel activity patterns of the piriform cortex, a part of the primary olfactory cortex, have been shown to represent odor perception, it remains unclear whether semantic contexts modulate odor representation in this region. Here, we investigated whether multi-voxel activity patterns in the piriform cortex change when semantic context modulates odor perception and, if so, whether the modulated areas communicate with brain regions involved in semantic and memory processing beyond the piriform cortex. We also explored regional differences within the piriform cortex, which are influenced by olfactory input and semantic context. We used 2 × 2 combinations of word labels and odorants that were perceived as congruent and measured piriform activity with a 1-mm isotropic resolution using 7T MRI. We found that identical odorants labeled with different words were perceived differently. This labeling effect was observed in multi-voxel activity patterns in the piriform cortex, as the searchlight decoding analysis distinguished identical odors with different labels for half of the examined stimulus pairs. Significant functional connectivity was observed between parts of the piriform cortex that were modulated by labels and regions associated with semantic and memory processing. While the piriform multi-voxel patterns evoked by different olfactory inputs were also distinguishable, the decoding accuracy was significant for only one stimulus pair, preventing definitive conclusions regarding the locational differences between areas influenced by word labels and olfactory inputs. These results suggest that multi-voxel patterns of piriform activity can be modulated by semantic context, possibly due to communication between the piriform cortex and the semantic and memory regions.


Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Odorantes , Percepção Olfatória , Córtex Piriforme , Semântica , Humanos , Masculino , Córtex Piriforme/fisiologia , Córtex Piriforme/diagnóstico por imagem , Percepção Olfatória/fisiologia , Feminino , Adulto , Adulto Jovem
4.
J Biol Chem ; 298(11): 102573, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36209821

RESUMO

Insect gustatory receptors play roles in sensing tastants, such as sugars and bitter substances. We previously demonstrated that the BmGr9 silkworm gustatory receptor is a d-fructose-gated ion channel receptor. However, the molecular mechanism of how d-fructose could initiate channel opening were unclear. Herein, we present a structural model for a channel pore and a d-fructose-binding site in BmGr9. Since the membrane topology and oligomeric state of BmGr9 appeared to be similar to those of an insect odorant receptor coreceptor, Orco, we constructed a structural model of BmGr9 based on the cryo-EM Orco structure. Our site-directed mutagenesis data suggested that the transmembrane region 7 forms channel pore and controls channel gating. This model also suggested that a pocket formed by transmembrane helices 2 to 4 and 6 binds d-fructose. Using mutagenesis experiments in combination with docking simulations, we were able to determine the potent binding mode of d-fructose. Finally, based on these data, we propose a conformational change that leads to channel opening upon d-fructose binding. Taken together, these findings detail the molecular mechanism by which an insect gustatory receptor can be activated by its ligand molecule.


Assuntos
Proteínas de Drosophila , Receptores Odorantes , Animais , Ligantes , Receptores Odorantes/metabolismo , Proteínas de Drosophila/genética , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Insetos/metabolismo , Frutose/metabolismo , Modelos Estruturais
5.
Chem Senses ; 482023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36625229

RESUMO

Humans have significant individual variations in odor perception, derived from their experience or sometimes from differences in the olfactory receptor (OR) gene repertoire. In several cases, the genetic variation of a single OR affects the perception of its cognate odor ligand. Musks are widely used for fragrance and are known to demonstrate specific anosmia. It, however, remains to be elucidated whether the OR polymorphism contributes to individual variations in musk odor perception. Previous studies reported that responses of the human musk receptor OR5AN1 to a variety of musks in vitro correlated well with perceptual sensitivity to those odors in humans and that the mouse ortholog, Olfr1440 (MOR215-1), plays a critical role in muscone perception. Here, we took advantage of genetic variation in OR5AN1 to examine how changes in receptor sensitivity are associated with human musk perception. We investigated the functional differences between OR5AN1 variants in an in vitro assay and measured both perceived intensity and detection threshold in human subjects with different OR5AN1 genotypes. Human subjects homozygous for the more sensitive L289F allele had a lower detection threshold for muscone and found macrocyclic musks to be more intense than subjects homozygous for the reference allele. These results demonstrate that the genetic variation in OR5AN1 contributes to perceptual differences for some musks. In addition, we found that the more functional variant of OR5A1, a receptor involved in ß-ionone perception, is associated with the less functional variant of OR5AN1, suggesting that the perceived intensities of macrocyclic musks and ß-ionone are inversely correlated.


Assuntos
Percepção Olfatória , Receptores Odorantes , Humanos , Camundongos , Animais , Receptores Odorantes/genética , Odorantes , Variação Genética , Percepção , Percepção Olfatória/genética , Receptores Colinérgicos/genética , Receptores Proteína Tirosina Quinases/genética
6.
Biosci Biotechnol Biochem ; 87(6): 646-648, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-36990645

RESUMO

Silkworm (Bombyx mori), an insect herbivore, is attracted to cis-jasmone released from mulberry leaves. Its olfactory receptor, BmOr56, specifically responds to cis-jasmone. In this study, we constructed a BmOr56 deletion line and found that the attractive behavior of cis-jasmone was completely lost in the mutant, suggesting the involvement of a single receptor in this specific chemoattractive behavior.


Assuntos
Bombyx , Receptores Odorantes , Animais , Bombyx/genética , Receptores Odorantes/genética , Quimiotaxia , Insetos , Proteínas de Insetos/genética
7.
Mol Biol Evol ; 38(2): 634-649, 2021 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-32961551

RESUMO

The exocrine-gland secreting peptide (ESP)gene family encodes proteinaceous pheromones that are recognized by the vomeronasal organ in mice. For example, ESP1 is a male pheromone secreted in tear fluid that regulates socio-sexual behavior, and ESP22 is a juvenile pheromone that suppresses adult sexual behavior. The family consists of multiple genes and has been identified only in mouse and rat genomes. The coding region of a mouse ESP gene is separated into two exons, each encoding signal and mature sequences. Here, we report the origin and evolution of the ESP gene family. ESP genes were found only in the Muridea and Cricetidae families of rodents, suggesting a recent origin of ESP genes in the common ancestor of murids and cricetids. ESP genes show a great diversity in number, length, and sequence among different species as well as mouse strains. Some ESPs in rats and golden hamsters are expressed in the lacrimal gland and the salivary gland. We also found that a mature sequence of an ESP gene showed overall sequence similarity to the α-globin gene. The ancestral ESP gene seems to be generated by recombination of a retrotransposed α-globin gene with the signal-encoding exon of the CRISP2 gene located adjacent to the ESP gene cluster. This study provides an intriguing example of molecular tinkering in rapidly evolving species-specific proteinaceous pheromone genes.


Assuntos
Evolução Molecular , Família Multigênica , Feromônios/genética , Roedores/genética , Animais , Cricetinae , Camundongos , Ratos
8.
J Biol Chem ; 294(7): 2256-2266, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30593507

RESUMO

Field studies have shown that plants growing next to herbivore-infested plants acquire higher resistance to herbivore damage. This increased resistance is partly due to regulation of plant gene expression by volatile organic compounds (VOCs) released by plants that sense environmental challenges such as herbivores. The molecular basis for VOC sensing in plants, however, is poorly understood. Here, we report the identification of TOPLESS-like proteins (TPLs) that have VOC-binding activity and are involved in VOC sensing in tobacco. While screening for volatiles that induce stress-responsive gene expression in tobacco BY-2 cells and tobacco plants, we found that some sesquiterpenes induce the expression of stress-responsive genes. These results provided evidence that plants sense these VOCs and motivated us to analyze the mechanisms underlying volatile sensing using tobacco as a model system. Using a pulldown assay with caryophyllene derivative-linked beads, we identified TPLs as transcriptional co-repressors that bind volatile caryophyllene analogs. Overexpression of TPLs in cultured BY-2 cells or tobacco leaves reduced caryophyllene-induced gene expression, indicating that TPLs are involved in the responses to caryophyllene analogs in tobacco. We propose that unlike animals, which use membrane receptors for sensing odorants, a transcriptional co-repressor plays a role in sensing and mediating VOC signals in plant cells.


Assuntos
Regulação da Expressão Gênica de Plantas/fisiologia , Nicotiana , Proteínas de Plantas , Transdução de Sinais/fisiologia , Estresse Fisiológico/fisiologia , Transcrição Gênica/fisiologia , Compostos Orgânicos Voláteis/metabolismo , Células Vegetais/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Nicotiana/genética , Nicotiana/metabolismo
9.
Chem Senses ; 45(1): 37-44, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31711116

RESUMO

Atypical sensory reactivities are pervasive among people with autism spectrum disorder (ASD). With respect to olfaction, most previous studies have used psychophysical or questionnaire-based methodologies; thus, the neural basis of olfactory processing in ASD remains unclear. This study aimed to determine the stages of olfactory processing that are altered in ASD. Fourteen young adults with high-functioning ASD (mean age, 21 years; 3 females) were compared with 19 age-matched typically developing (TD) controls (mean age, 21 years; 4 females). Olfactory event-related potentials (OERPs) for 2-phenylethyl alcohol-a rose-like odor-were measured with 64 scalp electrodes while participants performed a simple odor detection task. Significant group differences in OERPs were found in 3 time windows 542 ms after the stimulus onset. The cortical source activities in these time windows, estimated using standardized low-resolution brain electromagnetic tomography, were significantly higher in ASD than in TD in and around the posterior cingulate cortex, which is known to play a crucial role in modality-general cognitive processing. Supplemental Bayesian analysis provided substantial evidence for an alteration in the later stages of olfactory processing, whereas conclusive evidence was not provided for the earlier stages. These results suggest that olfactory processing in ASD is altered at least at the later, modality-general processing stage.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/psicologia , Potenciais Evocados , Olfato/fisiologia , Adolescente , Adulto , Transtorno do Espectro Autista/diagnóstico , Eletrodos , Feminino , Humanos , Masculino , Odorantes/análise , Álcool Feniletílico/análise , Adulto Jovem
10.
Chem Senses ; 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32441744

RESUMO

In response to the COVID-19 pandemic, countries have implemented various strategies to reduce and slow the spread of the disease in the general population. For countries that have implemented restrictions on its population in a step-wise manner, monitoring of COVID-19 prevalence is of importance to guide decision on when to impose new, or when to abolish old, restrictions. We are here determining whether measures of odor intensity in a large sample can serve as one such measure. Online measures of how intense common household odors are perceived and symptoms of COVID-19 were collected from 2440 Swedes. Average odor intensity ratings were then compared to predicted COVID-19 population prevalence over time in the Swedish population and were found to closely track each other (r=-0.83). Moreover, we found that there was a large difference in rated intensity between individuals with and without COVID-19 symptoms and number of symptoms was related to odor intensity ratings. Finally, we found that individuals progressing from reporting no symptoms to subsequently reporting COVID-19 symptoms demonstrated a large drop in olfactory performance. These data suggest that measures of odor intensity, if obtained in a large and representative sample, can be used as an indicator of COVID-19 disease in the general population. Importantly, this simple measure could easily be implemented in countries without widespread access to COVID-19 testing or implemented as a fast early response before wide-spread testing can be facilitated.

11.
Mol Biol Evol ; 35(6): 1437-1450, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29659972

RESUMO

Primates have traditionally been regarded as vision-oriented animals with low olfactory ability, though this "microsmatic primates" view has been challenged recently. To clarify when and how degeneration of the olfactory system occurred and to specify the relevant factors during primate evolution, we here examined the olfactory receptor (OR) genes from 24 phylogenetically and ecologically diverse primate species. The results revealed that strepsirrhines with curved noses had functional OR gene repertoires that were nearly twice as large as those for haplorhines with simple noses. Neither activity pattern (nocturnal/diurnal) nor color vision system showed significant correlation with the number of functional OR genes while phylogeny and nose structure (haplorhine/strepsirrhine) are statistically controlled, but extent of folivory did. We traced the evolutionary fates of individual OR genes by identifying orthologous gene groups, demonstrating that the rates of OR gene losses were accelerated at the ancestral branch of haplorhines, which coincided with the acquisition of acute vision. The highest rate of OR gene loss was observed at the ancestral branch of leaf-eating colobines; this reduction is possibly linked with the dietary transition from frugivory to folivory because odor information is essential for fruit foraging but less so for leaf foraging. Intriguingly, we found accelerations of OR gene losses in an external branch to every hominoid species examined. These findings suggest that the current OR gene repertoire in each species has been shaped by a complex interplay of phylogeny, anatomy, and habitat; therefore, multiple factors may contribute to the olfactory degeneration in primates.


Assuntos
Evolução Biológica , Primatas/genética , Receptores Odorantes/genética , Animais , Comportamento Alimentar , Visão Ocular
12.
Chem Senses ; 44(7): 465-481, 2019 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-31254383

RESUMO

In this study, we examined the mode of metabolism of food odorant molecules in the human nasal/oral cavity in vitro and in vivo. We selected 4 odorants, 2-furfurylthiol (2-FT), hexanal, benzyl acetate, and methyl raspberry ketone, which are potentially important for designing food flavors. In vitro metabolic assays of odorants with saliva/nasal mucus analyzed by gas chromatography mass spectrometry revealed that human saliva and nasal mucus exhibit the following 3 enzymatic activities: (i) methylation of 2-FT into furfuryl methylsulfide (FMS); (ii) reduction of hexanal into hexanol; and (iii) hydrolysis of benzyl acetate into benzyl alcohol. However, (iv) demethylation of methyl raspberry ketone was not observed. Real-time in vivo analysis using proton transfer reaction-mass spectrometry demonstrated that the application of 2-FT and hexanal through 3 different pathways via the nostril or through the mouth generated the metabolites FMS and hexanol within a few seconds. The concentration of FMS and hexanol in the exhaled air was above the perception threshold. A cross-adaptation study based on the activation pattern of human odorant receptors suggested that this metabolism affects odor perception. These results suggest that some odorants in food are metabolized in the human nasal mucus/saliva, and the resulting metabolites are perceived as part of the odor quality of the substrates. Our results help improve the understanding of the mechanism of food odor perception and may enable improved design and development of foods in relation to odor.


Assuntos
Boca/metabolismo , Cavidade Nasal/metabolismo , Odorantes/análise , Receptores Odorantes/metabolismo , Humanos , Mucosa Nasal/metabolismo
13.
Nature ; 502(7471): 368-71, 2013 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-24089208

RESUMO

Animals display a repertoire of different social behaviours. Appropriate behavioural responses depend on sensory input received during social interactions. In mice, social behaviour is driven by pheromones, chemical signals that encode information related to age, sex and physiological state. However, although mice show different social behaviours towards adults, juveniles and neonates, sensory cues that enable specific recognition of juvenile mice are unknown. Here we describe a juvenile pheromone produced by young mice before puberty, termed exocrine-gland secreting peptide 22 (ESP22). ESP22 is secreted from the lacrimal gland and released into tears of 2- to 3-week-old mice. Upon detection, ESP22 activates high-affinity sensory neurons in the vomeronasal organ, and downstream limbic neurons in the medial amygdala. Recombinant ESP22, painted on mice, exerts a powerful inhibitory effect on adult male mating behaviour, which is abolished in knockout mice lacking TRPC2, a key signalling component of the vomeronasal organ. Furthermore, knockout of TRPC2 or loss of ESP22 production results in increased sexual behaviour of adult males towards juveniles, and sexual responses towards ESP22-deficient juveniles are suppressed by ESP22 painting. Thus, we describe a pheromone of sexually immature mice that controls an innate social behaviour, a response pathway through the accessory olfactory system and a new role for vomeronasal organ signalling in inhibiting sexual behaviour towards young. These findings provide a molecular framework for understanding how a sensory system can regulate behaviour.


Assuntos
Feromônios/metabolismo , Comportamento Sexual Animal , Maturidade Sexual , Órgão Vomeronasal/metabolismo , Envelhecimento , Tonsila do Cerebelo/citologia , Animais , Feminino , Aparelho Lacrimal/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Feromônios/farmacologia , Células Receptoras Sensoriais/metabolismo , Comportamento Sexual Animal/efeitos dos fármacos , Canais de Cátion TRPC/deficiência , Canais de Cátion TRPC/genética , Canais de Cátion TRPC/metabolismo , Lágrimas/metabolismo , Órgão Vomeronasal/citologia
14.
Biosci Biotechnol Biochem ; 83(4): 705-708, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30516446
15.
Clin Calcium ; 28(8): 1124-1129, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30049923

RESUMO

Olfactory receptor(OR)genes constitute the largest gene family in mammals. Some of them have been shown to be expressed not only in the olfactory system, but also in various non-olfactory tissues. So far, the roles of such ectopically expressed ORs have been suggested mainly by in vitro experiments using cultured cells or tissues. Recently, analyses using OR knockout mice have revealed a few examples of important physiological functions outside the olfactory epithelium. An OR expressed in the carotid body senses the hypoxia and regulates breathing. An OR expressed in enterochromaffin(EC)cells in the gut senses microbial metabolites and induces a serotonin release to modulate serotonin-sensitive primary afferent neurons. These results suggest that ectopically expressed ORs sense an internal environmental change through chemical cues and modulate physiologically significant functions specific to each tissue where an OR is expressed. Further work will be required to understand their roles in other tissues.


Assuntos
Neurônios Receptores Olfatórios , Animais , Células Cultivadas , Camundongos , Camundongos Knockout , Receptores Odorantes
16.
J Neurosci ; 36(16): 4482-91, 2016 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-27098692

RESUMO

Musk odors have been used widely for fragrance and medicine for >2000 years because of their fascinating scent and physiological effects. Therefore, fragrance manufacturers have been eager to develop high-quality musk compounds that are safe and easily synthesized. We recently identified muscone-responsive olfactory receptors (ORs) MOR215-1 and OR5AN1 in mice and humans, respectively (Shirasu et al., 2014). In this study, we identified musk ORs that are evolutionarily closely related to MOR215-1 or OR5AN1 in various primates and investigated structure-activity relationships for various musk odorants and related compounds. We found that each species has one or two functional musk ORs that exhibit specific ligand spectra to musk compounds. Some of them, including the human OR5AN1, responded to nitro musks with chemical properties distinct from muscone. The ligand specificity of OR5AN1 reflects the perception of musk odors in humans. Genetic deletion of MOR215-1 in mice resulted in drastic reduction of sensitivity to muscone, suggesting that MOR215-1 plays a critical role in muscone perception. Therefore, the current study reveals a clear link between the identified OR and muscone perception. Moreover, the strategy established for screening ligands for the muscone OR may facilitate the development of novel and commercially useful musk odors. SIGNIFICANCE STATEMENT: The long-sought musk odor receptor family in mammals was discovered and found to be well conserved and narrowly tuned to musk odors. In mice, deletion of the most sensitive musk receptor resulted in drastic reduction in sensitivity to muscone, demonstrating a strong link between receptor and odor perception. In humans, we found one musk receptor that recognized both macrocyclic and nitro musks that had distinct chemical structures. The structure-activity relationships were in a good agreement with human sensory perception and therefore may be used to develop novel musk aroma in fragrance fields. Finally, identification of a natural ligand(s) for musk receptors in mammals other than musk deer would reveal an evolutionarily pivotal role in each species in the future.


Assuntos
Evolução Molecular , Ácidos Graxos Monoinsaturados/farmacologia , Odorantes , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Deleção de Sequência/fisiologia , Olfato/fisiologia , Animais , Relação Dose-Resposta a Droga , Ácidos Graxos Monoinsaturados/química , Feminino , Células HEK293 , Humanos , Ligantes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Filogenia , Relação Estrutura-Atividade
17.
Genome Res ; 24(9): 1485-96, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25053675

RESUMO

Olfactory receptors (ORs) detect odors in the environment, and OR genes constitute the largest multigene family in mammals. Numbers of OR genes vary greatly among species--reflecting the respective species' lifestyles--and this variation is caused by frequent gene gains and losses during evolution. However, whether the extent of gene gains/losses varies among individual gene lineages and what might generate such variation is unknown. To answer these questions, we used a newly developed phylogeny-based method to classify >10,000 intact OR genes from 13 placental mammal species into 781 orthologous gene groups (OGGs); we then compared the OGGs. Interestingly, African elephants had a surprisingly large repertoire (∼ 2000) of functional OR genes encoded in enlarged gene clusters. Additionally, OR gene lineages that experienced more gene duplication had weaker purifying selection, and Class II OR genes have evolved more dynamically than those in Class I. Some OGGs were highly expanded in a lineage-specific manner, while only three OGGs showed complete one-to-one orthology among the 13 species without any gene gains/losses. These three OGGs also exhibited highly conserved amino acid sequences; therefore, ORs in these OGGs may have physiologically important functions common to every placental mammal. This study provides a basis for inferring OR functions from evolutionary trajectory.


Assuntos
Expansão das Repetições de DNA , Elefantes/genética , Evolução Molecular , Família Multigênica , Receptores Odorantes/genética , Animais , Filogenia , Especificidade da Espécie
18.
Horm Behav ; 94: 53-60, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28645693

RESUMO

Vocal communication in animals is important for ensuring reproductive success. Male mice emit song-like "ultrasonic vocalizations (USVs)" when they encounter female mice, and females show approach to the USVs. However, it is unclear whether USVs of male mice trigger female behavioral and endocrine responses in reproduction. In this study, we first investigated the relationship between the number of deliveries in breeding pairs for 4months and USVs syllables emitted from those paired males during 3min of sexual encounter with unfamiliar female mice. There was a positive correlation between these two indices, which suggests that breeding pairs in which males could emit USVs more frequently had more offspring. Further, we examined the effect of USVs of male mice on female sexual behavior. Female mice showed more approach behavior towards vocalizing males than devocalized males. Finally, to determine whether USVs of male mice could activate the neural system governing reproductive function in female mice, the activation of kisspeptin neurons, key neurons to drive gonadotropin-releasing hormone neurons in the hypothalamus, was examined using dual-label immunocytochemistry with cAMP response element-binding protein phosphorylation (pCREB). In the arcuate nucleus (Arc), the number of kisspeptin neurons expressing pCREB significantly increased after exposure to USVs of male as compared with noise exposure group. In conclusion, our results suggest that USVs of male mice promote fertility in female mice by activating both their approaching behavior and central kisspeptin neurons.


Assuntos
Corte , Hipotálamo , Kisspeptinas/metabolismo , Comportamento Sexual Animal/efeitos da radiação , Ondas Ultrassônicas , Vocalização Animal/fisiologia , Animais , Feminino , Hipotálamo/citologia , Hipotálamo/metabolismo , Hipotálamo/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Neurônios/metabolismo , Neurônios/efeitos da radiação , Comportamento Sexual Animal/fisiologia
19.
J Exp Biol ; 220(Pt 10): 1781-1786, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28254882

RESUMO

Manduca sexta females attract their mates with the release of a species-specific sex-pheromone blend, with bombykal (E,Z)-10,12-hexadecadienal and (E,E,Z)-10,12,14-hexadecatrienal being the two major components. Here, we searched for the hawkmoth bombykal receptor in heterologous expression systems. The putative pheromone receptor MsexOr1 coexpressed with MsexOrco in Xenopus oocytes elicited dose-dependent inward currents upon bombykal application (10-300 µmol l-1), and coexpressed in HEK293 and CHO cells caused bombykal-dependent increases in the intracellular free Ca2+ concentration. In addition, the bombykal receptor of Bombyx mori BmOr3 coexpressed with MsexOrco responded to bombykal (30-100 µmol l-1) with inward currents. In contrast, MsexOr4 coexpressed with MsexOrco responded neither to bombykal (30-100 µmol l-1) nor to the (E,E,Z)-10,12,14-hexadecatrienal mimic. Thus, MsexOr1, but not MsexOrco and probably not MsexOr4, is the bombykal-binding pheromone receptor in the hawkmoth. Finally, we obtained evidence that phospholipase C and protein kinase C activity are involved in the hawkmoth's bombykal-receptor-mediated Ca2+ signals in HEK293 and CHO cells.


Assuntos
Manduca/fisiologia , Receptores Odorantes , Atrativos Sexuais/farmacologia , Alcadienos/farmacologia , Animais , Bombyx , Sinalização do Cálcio , Cricetulus , Células HEK293 , Humanos , Manduca/citologia , Neurônios Receptores Olfatórios , Oócitos , Xenopus
20.
Nature ; 466(7302): 118-22, 2010 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-20596023

RESUMO

Various social behaviours in mice are regulated by chemical signals called pheromones that act through the vomeronasal system. Exocrine gland-secreting peptide 1 (ESP1) is a 7-kDa peptide that is released into male tear fluids and stimulates vomeronasal sensory neurons in female mice. Here, we describe the molecular and neural mechanisms that are involved in the decoding of ESP1 signals in the vomeronasal system, which leads to behavioural output in female mice. ESP1 is recognized by a specific vomeronasal receptor, V2Rp5, and the ligand-receptor interaction results in sex-specific signal transmission to the amygdaloid and hypothalamic nuclei via the accessory olfactory bulb. Consequently, ESP1 enhances female sexual receptive behaviour upon male mounting (lordosis), allowing successful copulation. In V2Rp5-deficient mice, ESP1 induces neither neural activation nor sexual behaviour. These findings show that ESP1 is a crucial male pheromone that regulates female reproductive behaviour through a specific receptor in the mouse vomeronasal system.


Assuntos
Feromônios/metabolismo , Proteínas/metabolismo , Receptores Odorantes/metabolismo , Receptores de Feromônios/metabolismo , Comportamento Sexual Animal/fisiologia , Órgão Vomeronasal/metabolismo , Animais , Encéfalo/citologia , Encéfalo/metabolismo , Feminino , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Receptores Odorantes/deficiência , Receptores Odorantes/genética , Receptores de Feromônios/deficiência , Receptores de Feromônios/genética , Canais de Cátion TRPC/deficiência , Órgão Vomeronasal/citologia , Órgão Vomeronasal/inervação
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