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1.
Sci Rep ; 14(1): 15046, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951601

RESUMO

The cotton whitefly, Bemisia tabaci, is considered as a species complex with 46 cryptic species, with Asia II-1 being predominant in Asia. This study addresses a significant knowledge gap in the characterization of odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) in Asia II-1. We explored the expression patterns of OBPs and CSPs throughout their developmental stages and compared the motif patterns of these proteins. Significant differences in expression patterns were observed for the 14 OBPs and 14 CSPs of B. tabaci Asia II-1, with OBP8 and CSP4 showing higher expression across the developmental stages. Phylogenetic analysis reveals that OBP8 and CSP4 form distinct clades, with OBP8 appearing to be an ancestral gene, giving rise to the evolution of other odorant-binding proteins in B. tabaci. The genomic distribution of OBPs and CSPs highlights gene clustering on the chromosomes, suggesting functional conservation and evolutionary events following the birth-and-death model. Molecular docking studies indicate strong binding affinities of OBP8 and CSP4 with various odour compounds like ß-caryophyllene, α-pinene, ß-pinene and limonene, reinforcing their roles in host recognition and reproductive functions. This study elaborates on our understanding of the putative roles of different OBPs and CSPs in B. tabaci Asia II-1, hitherto unexplored. The dynamics of the expression of OBPs and CSPs and their interactions with odour compounds offer scope for developing innovative methods for controlling this global invasive pest.


Assuntos
Hemípteros , Proteínas de Insetos , Filogenia , Receptores Odorantes , Animais , Hemípteros/metabolismo , Hemípteros/genética , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Receptores Odorantes/química , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/química , Regulação da Expressão Gênica no Desenvolvimento , Simulação de Acoplamento Molecular , Sesquiterpenos Policíclicos/metabolismo , Limoneno/metabolismo , Sesquiterpenos/metabolismo
2.
Gigascience ; 132024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-39028585

RESUMO

Sex role differentiation is a widespread phenomenon. Sex pheromones are often associated with sex roles and convey sex-specific information. In Lepidoptera, females release sex pheromones to attract males, which evolve sophisticated olfactory structures to relay pheromone signals. However, in some primitive moths, sex role differentiation becomes diverged. Here, we introduce the chromosome-level genome assembly from ancestral Himalaya ghost moths, revealing a unique olfactory evolution pattern and sex role parity among Lepidoptera. These olfactory structures of the ghost moths are characterized by a dense population of trichoid sensilla, both larger male and female antennal entry parts of brains, compared to the evolutionary later Lepidoptera. Furthermore, a unique tandem of 34 odorant receptor 19 homologs in Thitarodes xiaojinensis (TxiaOr19) has been identified, which presents overlapped motifs with pheromone receptors (PRs). Interestingly, the expanded TxiaOr19 was predicted to have unconventional tuning patterns compared to canonical PRs, with nonsexual dimorphic olfactory neuropils discovered, which contributes to the observed equal sex roles in Thitarodes adults. Additionally, transposable element activity bursts have provided traceable loci landscapes where parallel diversifications occurred between TxiaOr19 and PRs, indicating that the Or19 homolog expansions were diversified to PRs during evolution and thus established the classic sex roles in higher moths. This study elucidates an olfactory prototype of intermediate sex communication from Himalaya ghost moths.


Assuntos
Mariposas , Animais , Mariposas/genética , Mariposas/fisiologia , Masculino , Feminino , Atrativos Sexuais/metabolismo , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Receptores de Feromônios/genética , Receptores de Feromônios/metabolismo , Filogenia , Comportamento Sexual Animal
3.
Sci Rep ; 14(1): 15502, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969768

RESUMO

This research focused on analyzing gene expression changes in the periodontal ligament (PDL) after tooth re-plantation to identify key genes and pathways involved in healing and regeneration. Utilizing a mouse model, mRNA was extracted from the PDL at various intervals post-replantation for RNA sequencing analysis, spanning from 3 to 56 days. The results revealed significant shifts in gene expression, particularly notable on day 28, supported by hierarchical clustering and principal component analysis. Gene ontology (GO) enrichment analysis highlighted an upregulation in olfactory receptor and G protein-coupled receptor signaling pathways at this time point. These findings were validated through reverse transcription-quantitative PCR (RT-qPCR), with immunochemical staining localizing olfactory receptor gene expression to the PDL and surrounding tissues. Moreover, a scratch assay indicated that olfactory receptor genes might facilitate wound healing in human PDL fibroblasts. These results underscore the importance of the 28-day post-transplant phase as a potential "tipping point" in PDL healing and regeneration. In conclusion, this research sheds light on the potential role of olfactory receptor genes in PDL regeneration, providing a foundation for developing new therapeutic approaches in tooth replantation and transplantation, with broader implications for regenerative medicine in oral health.


Assuntos
Ligamento Periodontal , Regeneração , Reimplante Dentário , Animais , Ligamento Periodontal/metabolismo , Camundongos , Reimplante Dentário/métodos , Regeneração/genética , Cicatrização/genética , Humanos , Masculino , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Fibroblastos/metabolismo , Modelos Animais de Doenças
4.
PeerJ ; 12: e17631, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006026

RESUMO

Background: Human olfactory receptors (ORs) account for approximately 60% of all human G protein-coupled receptors. The functions of ORs extend beyond olfactory perception and have garnered significant attention in tumor biology. However, a comprehensive pan-cancer analysis of ORs in human cancers is lacking. Methods: Using data from public databases, such as HPA, TCGA, GEO, GTEx, TIMER2, TISDB, UALCAN, GEPIA2, and GSCA, this study investigated the role of olfactory receptor family 7 subfamily A member 5 (OR7A5) in various cancers. Functional analysis of OR7A5 in LGG and GBM was performed using the CGGA database. Molecular and cellular experiments were performed to validate the expression and biological function of OR7A5 in gliomas. Results: The results revealed heightened OR7A5 expression in certain tumors, correlating with the expression levels of immune checkpoints and immune infiltration. In patients with gliomas, the expression levels of OR7A5 were closely associated with adverse prognosis, 1p/19p co-deletion status, and wild-type IDH status. Finally, in vitro experiments confirmed the inhibitory effect of OR7A5 knockdown on the proliferative capacity of glioma cells and on the expression levels of proteins related to lipid metabolism. Conclusion: This study establishes OR7A5 as a novel biomarker, potentially offering a novel therapeutic target for gliomas.


Assuntos
Biomarcadores Tumorais , Neoplasias Encefálicas , Glioma , Receptores Odorantes , Humanos , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Glioma/imunologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/imunologia , Linhagem Celular Tumoral , Prognóstico , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica
5.
J Agric Food Chem ; 72(28): 15865-15874, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38955350

RESUMO

Geosmin, a ubiquitous volatile sesquiterpenoid of microbiological origin, is causative for deteriorating the quality of many foods, beverages, and drinking water, by eliciting an undesirable "earthy/musty" off-flavor. Moreover, and across species from worm to human, geosmin is a volatile, chemosensory trigger of both avoidance and attraction behaviors, suggesting its role as semiochemical. Volatiles typically are detected by chemosensory receptors of the nose, which have evolved to best detect ecologically relevant food-related odorants and semiochemicals. An insect receptor for geosmin was recently identified in flies. A human geosmin-selective receptor, however, has been elusive. Here, we report on the identification and characterization of a human odorant receptor for geosmin, with its function being conserved in orthologs across six mammalian species. Notably, the receptor from the desert-dwelling kangaroo rat showed a more than 100-fold higher sensitivity compared to its human ortholog and detected geosmin at low nmol/L concentrations in extracts from geosmin-producing actinomycetes.


Assuntos
Naftóis , Receptores Odorantes , Sesquiterpenos , Animais , Humanos , Naftóis/metabolismo , Naftóis/química , Naftóis/análise , Sesquiterpenos/metabolismo , Sesquiterpenos/análise , Sesquiterpenos/química , Receptores Odorantes/metabolismo , Receptores Odorantes/genética , Receptores Odorantes/química , Ratos , Feromônios/metabolismo , Feromônios/química , Feromônios/análise , Odorantes/análise
6.
Proc Natl Acad Sci U S A ; 121(30): e2401926121, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39018190

RESUMO

Sex pheromones play a crucial role in mate location and reproductive success. Insects face challenges in finding mates in low-density environments. The population dynamics of locusts vary greatly, ranging from solitary individuals to high-density swarms, leading to multiple-trait divergence between solitary and gregarious phases. However, differences in sexual communication between solitary and gregarious locusts have not been sufficiently explored. Herein, we found that solitary locusts but not gregarious ones heavily rely on a single compound, dibutyl phthalate (DBP), for sexual communication. DBP is abundantly released by solitary female locusts and elicits strong attraction of male solitary and gregarious locusts. Solitary adult males display much higher electrophysiological responses to DBP than adult females. Additionally, LmigOr13 was identified as the DBP-specific odorant receptor expressed in neurons housed in basiconic sensilla. Male LmigOr13-/- mutants generated by CRISPR/Cas9 have low electrophysiological responses and behavioral attraction to DBP in both laboratory and field cage experiments. Notably, the attractiveness of DBP to male locusts becomes more evident at lower population densities imposed by controlling the cage size. This finding sheds light on the utilization of a sex pheromone to promote reproductive success in extremely low-density conditions and provides important insights into alternative approaches for population monitoring of locusts.


Assuntos
Dibutilftalato , Comportamento Sexual Animal , Animais , Feminino , Masculino , Comportamento Sexual Animal/fisiologia , Atrativos Sexuais/metabolismo , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Comunicação Animal
7.
Sci Rep ; 14(1): 16541, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39019908

RESUMO

The red palm weevil (RPW), Rhynchophorus ferrugineus (Olivier), also known as the Asian palm weevil, is an invasive pest that causes widespread damage to palm trees around the globe. As pheromone communication is crucial for their mass attack and survival on palm trees, the olfactory concept of pest control strategies has been widely explored recently. We aim to understand the molecular basis of olfaction in RPW by studying one of the key olfactory proteins in insect pheromone communication, sensory neuron membrane proteins (SNMPs). SNMPs belong to the CD36 (cluster of differentiation 36) family that perform two distinct olfactory roles in insects, either in pheromone (odorant) transfer to the odorant receptors (SNMP1) or in the pheromone clearing process (SNMP2). In this study, we performed antennal transcriptomic screening and identified six SNMPs, mapping them on the R. ferrugineus genome, and confirmed four distinct SNMPs. Both SNMP1 proteins in RPW, viz., RferSNMPu1 and RferSNMPu2, were mapped onto the same scaffold in different loci in the RPW genome. To further understand the function of these proteins, we first classified them using phylogenetic analysis and checked their tissue-specific expression patterns. Further, we measured the relative transcript abundance of SNMPs in laboratory-reared, field-collected adults and pheromone-exposure experiments, ultimately identifying RferSNMPu1 as a potential candidate for functional analysis. We mapped RferSNMPu1 expression in the antennae and found that expression patterns were similar in both sexes. We used RNAi-based gene silencing to knockdown RferSNMPu1 and tested the changes in the RPW responses to aggregation pheromone compounds, 4-methyl-5-nonanol (ferrugineol) and 4-methyl-5-nonanone (ferrugineone), and a kairomone, ethyl acetate using electroantennogram (EAG) recordings. We found a significant reduction in the EAG recordings in the RferSNMPu1 knockdown strain of adult RPWs, confirming its potential role in pheromone detection. The structural modelling revealed the key domains in the RferSNMPu1 structure, which could likely be involved in pheromone detection based on the identified ectodomain tunnels. Our studies on RferSNMPu1 with a putative role in pheromone detection provide valuable insight into understanding the olfaction in R. ferrugineus as well as in other Curculionids, as SNMPs are under-explored in terms of its functional role in insect olfaction. Most importantly, RferSNMPu1 can be used as a potential target for the olfactory communication disruption in the R. ferrugineus control strategies.


Assuntos
Proteínas de Insetos , Feromônios , Gorgulhos , Animais , Gorgulhos/metabolismo , Gorgulhos/genética , Feromônios/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Antenas de Artrópodes/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Masculino , Feminino , Inativação Gênica , Filogenia , Células Receptoras Sensoriais/metabolismo
8.
Parasit Vectors ; 17(1): 308, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026238

RESUMO

BACKGROUND: Lucilia cuprina (Wiedemann, 1830) (Diptera: Calliphoridae) is the main causative agent of flystrike of sheep in Australia and New Zealand. Female flies lay eggs in an open wound or natural orifice, and the developing larvae eat the host's tissues, a condition called myiasis. To improve our understanding of host-seeking behavior, we quantified gene expression in male and female antennae based on their behavior. METHODS: A spatial olfactometer was used to evaluate the olfactory response of L. cuprina mated males and gravid females to fresh or rotting beef. Antennal RNA-Seq analysis was used to identify sensory receptors differentially expressed between groups. RESULTS: Lucilia cuprina females were more attracted to rotten compared to fresh beef (> fivefold increase). However, males and some females did not respond to either type of beef. RNA-Seq analysis was performed on antennae dissected from attracted females, non-attracted females and males. Transcripts encoding sensory receptors from 11 gene families were identified above a threshold (≥ 5 transcript per million) including 49 ATP-binding cassette transporters (ABCs), two ammonium transporters (AMTs), 37 odorant receptors (ORs), 16 ionotropic receptors (IRs), 5 gustatory receptors (GRs), 22 odorant-binding proteins (OBPs), 9 CD36-sensory neuron membrane proteins (CD36/SNMPs), 4 chemosensory proteins (CSPs), 4 myeloid lipid-recognition (ML) and Niemann-Pick C2 disease proteins (ML/NPC2), 2 pickpocket receptors (PPKs) and 3 transient receptor potential channels (TRPs). Differential expression analyses identified sex-biased sensory receptors. CONCLUSIONS: We identified sensory receptors that were differentially expressed between the antennae of both sexes and hence may be associated with host detection by female flies. The most promising for future investigations were as follows: an odorant receptor (LcupOR46) which is female-biased in L. cuprina and Cochliomyia hominivorax Coquerel, 1858; an ABC transporter (ABC G23.1) that was the sole sensory receptor upregulated in the antennae of females attracted to rotting beef compared to non-attracted females; a female-biased ammonia transporter (AMT_Rh50), which was previously associated with ammonium detection in Drosophila melanogaster Meigen, 1830. This is the first report suggesting a possible role for ABC transporters in L. cuprina olfaction and potentially in other insects.


Assuntos
Antenas de Artrópodes , Calliphoridae , Perfilação da Expressão Gênica , Animais , Feminino , Masculino , Antenas de Artrópodes/metabolismo , Calliphoridae/genética , Miíase/veterinária , Miíase/parasitologia , Transcriptoma , Ovinos/parasitologia , Austrália , Nova Zelândia , Olfato , Receptores Odorantes/genética , Receptores Odorantes/metabolismo
9.
Sci Rep ; 14(1): 15408, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965271

RESUMO

Chemosensory impairment is an outstanding symptom of SARS-CoV-2 infections. We hypothesized that measured sensory impairments are accompanied by transcriptomic changes in the foliate papillae area of the tongue. Hospital personnel with known SARS-CoV-2 immunoglobulin G (IgG) status completed questionnaires on sensory perception (n = 158). A subcohort of n = 141 participated in forced choice taste tests, and n = 43 participants consented to donate tongue swabs of the foliate papillae area for whole transcriptome analysis. The study included four groups of participants differing in IgG levels (≥ 10 AU/mL = IgG+; < 10 AU/mL = IgG-) and self-reported sensory impairment (SSI±). IgG+ subjects not detecting metallic taste had higher IgG+ levels than IgG+ participants detecting iron gluconate (p = 0.03). Smell perception was the most impaired biological process in the transcriptome data from IgG+/SSI+ participants subjected to gene ontology enrichment. IgG+/SSI+ subjects demonstrated lower expression levels of 166 olfactory receptors (OR) and 9 taste associated receptors (TAS) of which OR1A2, OR2J2, OR1A1, OR5K1 and OR1G1, as well as TAS2R7 are linked to metallic perception. The question raised by this study is whether odorant receptors on the tongue (i) might play a role in metal sensation, and (ii) are potential targets for virus-initiated sensory impairments, which needs to be investigated in future functional studies.


Assuntos
COVID-19 , SARS-CoV-2 , Língua , Transcriptoma , Humanos , COVID-19/virologia , COVID-19/genética , COVID-19/metabolismo , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Língua/metabolismo , Língua/virologia , Língua/patologia , Imunoglobulina G , Metais/metabolismo , Papilas Gustativas/metabolismo , Percepção Gustatória/genética , Paladar , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Percepção Olfatória
10.
Int J Mol Sci ; 25(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-39000230

RESUMO

In insect olfaction, sensitization refers to the amplification of a weak olfactory signal when the stimulus is repeated within a specific time window. In the vinegar fly, Drosophila melanogaster, this occurs already at the periphery, at the level of olfactory sensory neurons (OSNs) located in the antenna. In our study, we investigate whether sensitization is a widespread property in a set of seven types of OSNs, as well as the mechanisms involved. First, we characterize and compare the differences in spontaneous activity, response velocity and response dynamics, among the selected OSN types. These express different receptors with distinct tuning properties and behavioral relevance. Second, we show that sensitization is not a general property. Among our selected OSN types, it occurs in those responding to more general food odors, while OSNs involved in very specific detection of highly specific ecological cues like pheromones and warning signals show no sensitization. Moreover, we show that mitochondria play an active role in sensitization by contributing to the increase in intracellular Ca2+ upon weak receptor activation. Thus, by using a combination of single sensillum recordings (SSRs), calcium imaging and pharmacology, we widen the understanding of how the olfactory signal is processed at the periphery.


Assuntos
Drosophila melanogaster , Neurônios Receptores Olfatórios , Olfato , Animais , Neurônios Receptores Olfatórios/fisiologia , Neurônios Receptores Olfatórios/metabolismo , Drosophila melanogaster/fisiologia , Olfato/fisiologia , Odorantes , Cálcio/metabolismo , Plasticidade Neuronal/fisiologia , Receptores Odorantes/metabolismo , Mitocôndrias/metabolismo
11.
Int J Mol Sci ; 25(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38892263

RESUMO

The cell surface metalloprotease ADAM17 (a disintegrin and metalloprotease 17) and its binding partners iRhom2 and iRhom1 (inactive Rhomboid-like proteins 1 and 2) modulate cell-cell interactions by mediating the release of membrane proteins such as TNFα (Tumor necrosis factor α) and EGFR (Epidermal growth factor receptor) ligands from the cell surface. Most cell types express both iRhoms, though myeloid cells exclusively express iRhom2, and iRhom1 is the main iRhom in the mouse brain. Here, we report that iRhom2 is uniquely expressed in olfactory sensory neurons (OSNs), highly specialized cells expressing one olfactory receptor (OR) from a repertoire of more than a thousand OR genes in mice. iRhom2-/- mice had no evident morphological defects in the olfactory epithelium (OE), yet RNAseq analysis revealed differential expression of a small subset of ORs. Notably, while the majority of ORs remain unaffected in iRhom2-/- OE, OSNs expressing ORs that are enriched in iRhom2-/- OE showed fewer gene expression changes upon odor environmental changes than the majority of OSNs. Moreover, we discovered an inverse correlation between the expression of iRhom2 compared to OSN activity genes and that odor exposure negatively regulates iRhom2 expression. Given that ORs are specialized G-protein coupled receptors (GPCRs) and many GPCRs activate iRhom2/ADAM17, we investigated if ORs could activate iRhom2/ADAM17. Activation of an olfactory receptor that is ectopically expressed in keratinocytes (OR2AT4) by its agonist Sandalore leads to ERK1/2 phosphorylation, likely via an iRhom2/ADAM17-dependent pathway. Taken together, these findings point to a mechanism by which odor stimulation of OSNs activates iRhom2/ADAM17 catalytic activity, resulting in downstream transcriptional changes to the OR repertoire and activity genes, and driving a negative feedback loop to downregulate iRhom2 expression.


Assuntos
Neurônios Receptores Olfatórios , Receptores Odorantes , Animais , Receptores Odorantes/metabolismo , Receptores Odorantes/genética , Camundongos , Neurônios Receptores Olfatórios/metabolismo , Olfato/fisiologia , Proteína ADAM17/metabolismo , Proteína ADAM17/genética , Camundongos Knockout , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Mucosa Olfatória/metabolismo , Regulação da Expressão Gênica , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Humanos
12.
Genesis ; 62(3): e23610, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38874301

RESUMO

The organization of the olfactory glomerular map involves the convergence of olfactory sensory neurons (OSNs) expressing the same odorant receptor (OR) into glomeruli in the olfactory bulb (OB). A remarkable feature of the olfactory glomerular map formation is that the identity of OR instructs the topography of the bulb, resulting in thousands of discrete glomeruli in mice. Several lines of evidence indicate that ORs control the expression levels of various kinds of transmembrane proteins to form glomeruli at appropriate regions of the OB. In this review, we will discuss how the OR identity is decoded by OSNs into gene expression through intracellular regulatory mechanisms.


Assuntos
Bulbo Olfatório , Neurônios Receptores Olfatórios , Receptores Odorantes , Animais , Camundongos , Bulbo Olfatório/metabolismo , Neurônios Receptores Olfatórios/metabolismo , Receptores Odorantes/genética , Receptores Odorantes/metabolismo
13.
Genesis ; 62(3): e23611, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38888221

RESUMO

Olfactory sensory neurons (OSNs) are one of a few neuron types that are generated continuously throughout life in mammals. The persistence of olfactory sensory neurogenesis beyond early development has long been thought to function simply to replace neurons that are lost or damaged through exposure to environmental insults. The possibility that olfactory sensory neurogenesis may also serve an adaptive function has received relatively little consideration, largely due to the assumption that the generation of new OSNs is stochastic with respect to OSN subtype, as defined by the single odorant receptor gene that each neural precursor stochastically chooses for expression out of hundreds of possibilities. Accordingly, the relative birthrates of different OSN subtypes are predicted to be constant and impervious to olfactory experience. This assumption has been called into question, however, by evidence that the birthrates of specific OSN subtypes can be selectively altered by manipulating olfactory experience through olfactory deprivation, enrichment, and conditioning paradigms. Moreover, studies of recovery of the OSN population following injury provide further evidence that olfactory sensory neurogenesis may not be strictly stochastic with respect to subtype. Here we review this evidence and consider mechanistic and functional implications of the prospect that specific olfactory experiences can regulate olfactory sensory neurogenesis rates in a subtype-selective manner.


Assuntos
Neurogênese , Neurônios Receptores Olfatórios , Receptores Odorantes , Animais , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Neurônios Receptores Olfatórios/metabolismo , Neurônios Receptores Olfatórios/fisiologia , Neurogênese/genética , Olfato/fisiologia , Olfato/genética , Humanos
14.
J Cell Mol Med ; 28(11): e18366, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38856956

RESUMO

Ischemic stroke is one of the main causes of disability and death. However, recanalization of occluded cerebral arteries is effective only within a very narrow time window. Therefore, it is particularly important to find neuroprotective biological targets for cerebral artery recanalization. Here, gene expression profiles of datasets GSE160500 and GSE97537 were downloaded from the GEO database, which were related to ischemic stroke in rats. Olfactory receptor 78 (Olfr78) was screened, and which highly associated with Calcium signalling pathway and MAPK pathway. Interacting protein of Olfr78, Prkaca, was predicted by STRING, and their interaction was validated by Co-IP analysis. Then, a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) and a neuronal cell model stimulated by oxygen-glucose deprivation/reoxygenation (OGD/R) were constructed, and the results showed that expression of Olfr78 and Prkaca was downregulated in MCAO rats and OGD/R-stimulated neurons. Overexpression of Olfr78 or Prkaca inhibited the secretion of inflammatory factors, Ca2+ overload, and OGD/R-induced neuronal apoptosis. Moreover, Overexpression of Prkaca increased protein levels of cAMP, PKA and phosphorylated p38 in OGD/R-stimulated neurons, while SB203580, a p38 inhibitor, treatment inhibited activation of the cAMP/PKA-MAPK pathway and counteracted the effect of Olfr78 overexpression on improvement of neuronal functions. Meanwhile, overexpression of Olfr78 or Prkaca markedly inhibited neuronal apoptosis and improved brain injury in MCAO/R rats. In conclusion, overexpression of Olfr78 inhibited Ca2+ overload and reduced neuronal apoptosis in MCAO/R rats by promoting Prkaca-mediated activation of the cAMP/PKA-MAPK pathway, thereby improving brain injury in cerebral ischaemia-reperfusion.


Assuntos
Apoptose , AMP Cíclico , Ratos Sprague-Dawley , Receptores Odorantes , Traumatismo por Reperfusão , Animais , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/genética , Ratos , Masculino , AMP Cíclico/metabolismo , Receptores Odorantes/metabolismo , Receptores Odorantes/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Lesões Encefálicas/metabolismo , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Neurônios/metabolismo , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/metabolismo , Transdução de Sinais
15.
Biochem Biophys Res Commun ; 726: 150273, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914041

RESUMO

Insect olfactory receptors (ORs) are seven-transmembrane domain ion channels that function by forming heteromeric complexes with olfactory receptor co-receptors (Orcos). In this study, we investigated the potential for enhancing sensitivity of odor detection and responsivity through genetic modification of Orcos, considering its wider application in odor sensing. First, we measured the intensity of response to 1-octen-3-ol for the mosquito Aedes aegypti OR (AaOR8) when complexed individually with an Orco from the same mosquito (AaOrco), the honeybee Apis mellifera (AmOrco), the silkworm Bombyx mori (BmOrco), or the fruit fly Drosophila melanogaster (DmOrco). Relative to the other Orcos, AmOrco demonstrated higher sensitivity and responsivity, with a 1.8 to 21-fold decrease in the half-maximal effective concentration (EC50) and a 1.6-8.8-fold increase in the maximal effect (Emax), respectively. Furthermore, AmOrco co-expressed with AaOR10, BmOR56, or DmOR47a showed higher sensitivity and responsivity than AaOrco, BmOrco, or DmOrco co-expressed with their respective ORs. To further increase sensitivity and responsivity, we engineered chimeric Orcos by fusing AmOrco with DmOrco, considering the domain characteristics of Orcos. The response to 1-octen-3-ol was evaluated for AaOR8 when complexed individually with AmOrco, as well as for a mutant that combines DmOrco from the N-terminal (NT) to the C-terminal region of the fourth transmembrane domain (TM4) with the region of AmOrco following TM4 (Dm[NT-TM4]AmOrco). When compared to AmOrco, Dm(NT-TM4)AmOrco showed higher sensitivity and responsivity, with a 1.4-fold decrease in the EC50 and a 1.4-fold increase in the Emax, respectively. In addition, Dm(NT-TM4)AmOrco co-expressed with either DmOR47a or BmOR56 demonstrated higher sensitivity and responsivity than AmOrco co-expressed with their respective ORs. These results suggest that AmOrco could be a relatively more sensitive Orco, and further enhancement of sensitivity and responsivity could be achieved through recombination with heterologous Orcos near the TM4 of AmOrco.


Assuntos
Odorantes , Receptores Odorantes , Animais , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Receptores Odorantes/química , Odorantes/análise , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Bombyx/genética , Bombyx/metabolismo , Aedes/genética , Aedes/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/química , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/química , Abelhas/metabolismo , Abelhas/genética , Células HEK293 , Octanóis
16.
Arch Biochem Biophys ; 758: 110061, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38880319

RESUMO

Indole is widely present in nature and contributes significantly to the smell of flowers and animal excretion. However, the odor perception mechanism for indole is unclear, despite previous reports suggesting that it activates the Olfr740 family of receptors. In this study, we successfully identified another receptor, Olfr205, that is responsive to indole. Molecular model construction and binding pocket analysis predicted that the A202 residue in transmembrane helix 5 of Olfr205 forms a crucial hydrogen bond with indole, facilitating receptor activation. Additionally, G112 in transmembrane helix 3 of the Olfr740 family is involved in indole activation of receptors. Finally, our mutant function assay showed that substitution of A202 in Olfr205 and G112 in Olfr740 with other amino acids significantly decreased the receptor response to indole, which provides robust evidence to confirm the docking results. In summary, our study is the first to reveal that Olfr205 is an olfactory receptor distinct from those in the Olfr740 family that is activated by indole. Moreover, these receptors display different indole-binding mechanisms. This study sheds light on molecular binding mechanisms and contributes to a deeper understanding of indole perception.


Assuntos
Indóis , Receptores Odorantes , Indóis/metabolismo , Indóis/química , Indóis/farmacologia , Receptores Odorantes/metabolismo , Receptores Odorantes/genética , Receptores Odorantes/química , Animais , Humanos , Células HEK293 , Simulação de Acoplamento Molecular , Sequência de Aminoácidos , Sítios de Ligação , Ligação Proteica
17.
PLoS One ; 19(6): e0306029, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38917199

RESUMO

Humans have approximately 400 different olfactory receptors (hORs) and recognize odorants through the repertoire of hOR responses. Although the cell surface expression of hORs is critical to evaluate their response, hORs are poorly expressed on the surface of heterologous cells. To address this problem, previous studies have focused on hOR transportation to the membrane. Nevertheless, the response pattern of hORs to odorants has yet to be successfully linked, and the response sensitivity still remains to be improved. In this study, we demonstrate that increasing the transcriptional level can result in a significant increase in cell surface and functional expression of hORs. We used the TAR-Tat system, which increases the transcription efficiency through positive feedback, and found that OR1A1, OR6N2, and OR51M1 exhibited robust expression. Moreover, this system induces enhanced hOR responses to odorants, thus defining four hORs as novel n-hexanal receptors and n-hexanal is an inverse agonist to one of them. Our results suggested that using the TAR-Tat system and increasing the transcriptional level of hORs can help understanding the relationship between hORs and odorants that were previously undetectable. This finding could facilitate the understanding of the sense of smell by decoding the repertoire of hOR responses.


Assuntos
Odorantes , Receptores Odorantes , Transcrição Gênica , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Humanos , Aldeídos/metabolismo , Aldeídos/farmacologia
18.
Science ; 384(6703): 1460-1467, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38870275

RESUMO

Most insects, including human-targeting mosquitoes, detect odors through odorant-activated ion channel complexes consisting of a divergent odorant-binding subunit (OR) and a conserved co-receptor subunit (Orco). As a basis for understanding how odorants activate these heteromeric receptors, we report here cryo-electron microscopy structures of two different heteromeric odorant receptor complexes containing ORs from disease-vector mosquitos Aedes aegypti or Anopheles gambiae. These structures reveal an unexpected stoichiometry of one OR to three Orco subunits. Comparison of structures in odorant-bound and unbound states indicates that odorant binding to the sole OR subunit is sufficient to open the channel pore, suggesting a mechanism of OR activation and a conceptual framework for understanding evolution of insect odorant receptor sensitivity.


Assuntos
Aedes , Anopheles , Microscopia Crioeletrônica , Proteínas de Insetos , Odorantes , Receptores Odorantes , Animais , Aedes/fisiologia , Anopheles/fisiologia , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Multimerização Proteica , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Receptores Odorantes/química , Receptores Odorantes/metabolismo
19.
Sci Adv ; 10(23): eadk9000, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38848359

RESUMO

Olfaction is essential for complex social behavior in insects. To discriminate complex social cues, ants evolved an expanded number of odorant receptor (Or) genes. Mutations in the obligate odorant co-receptor gene orco lead to the loss of ~80% of the antennal lobe glomeruli in the jumping ant Harpegnathos saltator. However, the cellular mechanism remains unclear. Here, we demonstrate massive apoptosis of odorant receptor neurons (ORNs) in the mid to late stages of pupal development, possibly due to ER stress in the absence of Orco. Further bulk and single-nucleus transcriptome analysis shows that, although most orco-expressing ORNs die in orco mutants, a small proportion of them survive: They express ionotropic receptor (Ir) genes that form IR complexes. In addition, we found that some Or genes are expressed in mechanosensory neurons and nonneuronal cells, possibly due to leaky regulation from nearby non-Or genes. Our findings provide a comprehensive overview of ORN development and Or expression in H. saltator.


Assuntos
Formigas , Neurônios Receptores Olfatórios , Receptores Odorantes , Animais , Neurônios Receptores Olfatórios/metabolismo , Formigas/genética , Formigas/metabolismo , Formigas/fisiologia , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Apoptose , Mutação , Sobrevivência Celular , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Perfilação da Expressão Gênica , Transcriptoma
20.
Science ; 384(6703): 1453-1460, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38870272

RESUMO

Insects detect and discriminate a diverse array of chemicals using odorant receptors (ORs), which are ligand-gated ion channels comprising a divergent odorant-sensing OR and a conserved odorant receptor co-receptor (Orco). In this work, we report structures of the ApOR5-Orco heterocomplex from the pea aphid Acyrthosiphon pisum alone and bound to its known activating ligand, geranyl acetate. In these structures, three ApOrco subunits serve as scaffold components that cannot bind the ligand and remain relatively unchanged. Upon ligand binding, the pore-forming helix S7b of ApOR5 shifts outward from the central pore axis, causing an asymmetrical pore opening for ion influx. Our study provides insights into odorant recognition and channel gating of the OR-Orco heterocomplex and offers structural resources to support development of innovative insecticides and repellents for pest control.


Assuntos
Acetatos , Afídeos , Proteínas de Insetos , Receptores Odorantes , Receptores Odorantes/química , Receptores Odorantes/metabolismo , Receptores Odorantes/genética , Animais , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Afídeos/química , Acetatos/química , Acetatos/metabolismo , Ligantes , Terpenos/química , Terpenos/metabolismo , Odorantes/análise , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Ativação do Canal Iônico , Microscopia Crioeletrônica , Monoterpenos Acíclicos
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