scholarly journals Non-canonical odor coding ensures unbreakable mosquito attraction to humans

2020 ◽  
Author(s):  
Meg A. Younger ◽  
Margaret Herre ◽  
Alison R. Ehrlich ◽  
Zhongyan Gong ◽  
Zachary N. Gilbert ◽  
...  
Keyword(s):  
Olfactory System ◽  
Receptor Gene ◽  
Gene Families ◽  
Receptor Expression ◽  
Olfactory Neurons ◽  
Odor Cues ◽  
Chemosensory Receptor ◽  
Single Receptor ◽  
The Brain

SUMMARYFemale Aedes aegypti mosquitoes show strong innate attraction to humans. This chemosensory behavior is critical to species survival because females require a blood-meal to reproduce. Humans, the preferred host of Ae. aegypti, produce a complex blend of odor cues along with carbon dioxide (CO2) that attracts females ready to bite. Mosquitoes detect these cues with heteromeric ligand-gated ion channels encoded by three different chemosensory receptor gene families. A common theme in other species is that olfactory neurons express a single receptor that defines their chemical specificity and that they extend axons that converge upon dedicated glomeruli in the first sensory processing center in the brain. Such an organization permits the brain to segregate olfactory information and monitor activity of individual glomeruli to interpret what smell has been encountered. We have discovered that Ae. aegypti uses an entirely different organizational principle for its olfactory system. Using genetic strains that label subpopulations of olfactory neurons, we found that many neurons co-express multiple members of at least two of the chemosensory receptor families. This unexpected co-expression is functional, as assessed by in vivo calcium imaging showing that a given glomerulus is activated by multiple ligands detected by different receptor families. This has direct functional consequences for mosquito behavior. Mutant mosquitoes that cannot sense CO2 can be behaviorally activated by a volatile amine that stimulates the CO2 glomerulus. This non-canonical olfactory system organization featuring overlapping receptor expression may explain the female mosquito’s robust and “unbreakable’ attraction to humans.

Hypercholesterolemia is associated with enhanced angiotensin AT1-receptor expression

1997 ◽  
Vol 272 (6) ◽  
pp. H2701-H2707 ◽  
Author(s):  
G. Nickenig ◽  
O. Jung ◽  
K. Strehlow ◽  
O. Zolk ◽  
W. Linz ◽  
...  
Keyword(s):  
New Zealand ◽  
Angiotensin Ii ◽  
Radioligand Binding ◽  
Receptor Gene ◽  
Density Lipoprotein ◽  
At1 Receptor ◽  
Receptor Expression ◽  
At1 Receptors ◽  
New Zealand White Rabbits

Low-density lipoprotein increases the AT1-receptor gene expression in vascular smooth muscle cells. To elucidate whether elevated cholesterol serum levels upregulate the AT1 receptor and its functional response to angiotensin II in vivo, we compared 1) the vasoconstrictive effect of angiotensin II and 2) the level of expression of the vascular AT1 receptor in aortas of normocholesterolemic and hypercholesterolemic rabbits. Contraction experiments on isolated aortic rings showed that the angiotensin II-induced vasoconstriction was increased in hypercholesterolemic New Zealand White rabbits compared with normocholesterolemic New Zealand White rabbits. This difference in the angiotensin II-induced vasoconstriction was caused by a twofold increase in the density of cell surface AT1 receptors in hypercholesterolemic rabbits, as assessed by radioligand binding assays. The enhanced expression of AT1 receptors on the surface of these vascular cells was caused by elevated steady-state levels of the AT1-receptor mRNA to 220 +/- 35% in aortas excised from hypercholesterolemic rabbits compared with levels in aortas from normocholesterolemic rabbits, as measured by Northern blot analysis. These data indicate that hypercholesterolemia is associated with upregulation of expression and function of vascular AT1 receptors in vivo. This suggests a novel mechanism by which hypercholesterolemia could be involved in the onset and progression of chronic vascular diseases such as hypertension and arteriosclerosis if the phenomenon is confirmed in humans.

scholarly journals CRDB: Database of Chemosensory Receptor Gene Families in Vertebrate

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e31540 ◽  
Author(s):  
Dong Dong ◽  
Ke Jin ◽  
Xiaoli Wu ◽  
Yang Zhong
Keyword(s):  
Receptor Gene ◽  
Gene Families ◽  
Chemosensory Receptor

scholarly journals Human Somatostatin SST4 Receptor Transgenic Mice: Construction and Brain Expression Pattern Characterization

2021 ◽  
Vol 22 (7) ◽  
pp. 3758
Author(s):  
Balázs Nemes ◽  
Kata Bölcskei ◽  
Angéla Kecskés ◽  
Viktória Kormos ◽  
Balázs Gaszner ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Regulatory Elements ◽  
Receptor Expression ◽  
Luciferase Reporter ◽  
Mouse Line ◽  
Humanized Mouse ◽  
Peripheral Tissues ◽  
And Function ◽  
The Brain

Somatostatin receptor subtype 4 (SST4) has been shown to mediate analgesic, antidepressant and anti-inflammatory functions without endocrine actions; therefore, it is proposed to be a novel target for drug development. To overcome the species differences of SST4 receptor expression and function between humans and mice, we generated an SST4 humanized mouse line to serve as a translational animal model for preclinical research. A transposon vector containing the hSSTR4 and reporter gene construct driven by the hSSTR4 regulatory elements were created. The vector was randomly inserted in Sstr4-deficient mice. hSSTR4 expression was detected by bioluminescent in vivo imaging of the luciferase reporter predominantly in the brain. RT-qPCR confirmed the expression of the human gene in the brain and various peripheral tissues consistent with the in vivo imaging. RNAscope in situ hybridization revealed the presence of hSSTR4 transcripts in glutamatergic excitatory neurons in the CA1 and CA2 regions of the hippocampus; in the GABAergic interneurons in the granular layer of the olfactory bulb and in both types of neurons in the primary somatosensory cortex, piriform cortex, prelimbic cortex and amygdala. This novel SST4 humanized mouse line might enable us to investigate the differences of human and mouse SST4 receptor expression and function and assess the effects of SST4 receptor agonist drug candidates.

scholarly journals Stabilization of the μ-Opioid Receptor by Truncated Single Transmembrane Splice Variants through a Chaperone-like Action

2013 ◽  
Vol 288 (29) ◽  
pp. 21211-21227 ◽  
Author(s):  
Jin Xu ◽  
Ming Xu ◽  
Taylor Brown ◽  
Grace C. Rossi ◽  
Yasmin L. Hurd ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Opioid Receptor ◽  
Splice Variants ◽  
Receptor Gene ◽  
Exon Skipping ◽  
Receptor Expression ◽  
Functional Roles ◽  
Μ Opioid Receptor ◽  
Tm Domain

The μ-opioid receptor gene, OPRM1, undergoes extensive alternative pre-mRNA splicing, as illustrated by the identification of an array of splice variants generated by both 5′ and 3′ alternative splicing. The current study reports the identification of another set of splice variants conserved across species that are generated through exon skipping or insertion that encodes proteins containing only a single transmembrane (TM) domain. Using a Tet-Off system, we demonstrated that the truncated single TM variants can dimerize with the full-length 7-TM μ-opioid receptor (MOR-1) in the endoplasmic reticulum, leading to increased expression of MOR-1 at the protein level by a chaperone-like function that minimizes endoplasmic reticulum-associated degradation. In vivo antisense studies suggested that the single TM variants play an important role in morphine analgesia, presumably through modulation of receptor expression levels. Our studies suggest the functional roles of truncated receptors in other G protein-coupled receptor families.

scholarly journals Evolving the Olfactory System with Machine Learning

2021 ◽  
Author(s):  
Peter Y Wang ◽  
Yi Sun ◽  
Richard Axel ◽  
LF Abbott ◽  
Guangyu Robert Yang
Keyword(s):  
Machine Learning ◽  
Neural Networks ◽  
Olfactory System ◽  
Convergent Evolution ◽  
Biological Mechanisms ◽  
Single Receptor ◽  
System Input ◽  
Functional Logic ◽  
Odor Classification

The convergent evolution of the fly and mouse olfactory system led us to ask whether the anatomic connectivity and functional logic in vivo would evolve in artificial neural networks constructed to perform olfactory tasks. Artificial networks trained to classify odor identity recapitulate the connectivity inherent in the olfactory system. Input units are driven by a single receptor type, and units driven by the same receptor converge to form a glomerulus. Glomeruli exhibit sparse, unstructured connectivity to a larger, expansion layer. When trained to both classify odor and impart innate valence on odors, the network develops independent pathways for innate output and odor classification. Thus, artificial networks evolve even without the biological mechanisms necessary to build these systems in vivo, providing a rationale for the convergent evolution of olfactory circuits.

scholarly journals Regulation of neuron-specific gene transcription by stress hormone signalling requires synaptic activity in zebrafish

2019 ◽  
Author(s):  
Helen Eachus ◽  
Dheemanth Subramanya ◽  
Harriet E. Jackson ◽  
Guannyu Wang ◽  
Kieran Berntsen ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Gene ◽  
Model Organism ◽  
Receptor Expression ◽  
Synaptic Activity ◽  
Specific Gene ◽  
Metabotropic Glutamate ◽  
Synaptic Neurotransmission ◽  
The Brain

AbstractThe Glucocorticoid Receptor (GR) co-ordinates metabolic and behavioural responses to stressors. We hypothesised that GR influences behaviour by modulating specific epigenetic and transcriptional processes in the brain. Using the zebrafish as a model organism, the brain methylomes of wild-type and grs357 mutant adults were analysed and GR-sensitive, differentially methylated regions (GR-DMRs) were identified. Two genes with GR-DMRs exhibited distinct methylation and transcriptional sensitivities to GR: the widely expressed direct GR target fkbp5 and neuron-specific aplp1. In larvae, neural activity is required for GR-mediated transcription of aplp1, but not for that of fkbp5. GR regulates metabotropic glutamate receptor gene expression, the activities of which also modulated aplp1 expression, implicating synaptic neurotransmission as an effector of GR function upstream of aplp1. Our results identify two distinct routes of GR-regulated transcription in the brain, including a pathway through which GR couples endocrine signalling to synaptic activity-regulated transcription by modulating metabotropic glutamate receptor expression.

scholarly journals The Divergent Orphan Nuclear Receptor ODR-7 Regulates Olfactory Neuron Gene Expression via Multiple Mechanisms in Caenorhabditis elegans

Genetics ◽  
2003 ◽  
Vol 165 (4) ◽  
pp. 1779-1791
Author(s):  
Marc E Colosimo ◽  
Susan Tran ◽  
Piali Sengupta
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Receptor Gene ◽  
Biological Processes ◽  
Orphan Nuclear Receptor ◽  
Olfactory Neurons ◽  
C Elegans

Abstract Nuclear receptors regulate numerous critical biological processes. The C. elegans genome is predicted to encode ∼270 nuclear receptors of which >250 are unique to nematodes. ODR-7 is the only member of this large divergent family whose functions have been defined genetically. ODR-7 is expressed in the AWA olfactory neurons and specifies AWA sensory identity by promoting the expression of AWA-specific signaling genes and repressing the expression of an AWC-specific olfactory receptor gene. To elucidate the molecular mechanisms of action of a divergent nuclear receptor, we have identified residues and domains required for different aspects of ODR-7 function in vivo. ODR-7 utilizes an unexpected diversity of mechanisms to regulate the expression of different sets of target genes. Moreover, these mechanisms are distinct in normal and heterologous cellular contexts. The odr-7 ortholog in the closely related nematode C. briggsae can fully substitute for all ODR-7-mediated functions, indicating conservation of function across 25–120 million years of divergence.

scholarly journals Regulation of nerve growth factor receptor gene expression in sympathetic neurons during development.

1995 ◽  
Vol 130 (6) ◽  
pp. 1435-1446 ◽  
Author(s):  
S Wyatt ◽  
A M Davies
Keyword(s):  
Mrna Expression ◽  
Sensory Neurons ◽  
Sympathetic Neurons ◽  
Receptor Gene ◽  
Receptor Expression ◽  
Early Developmental Stage ◽  
Mrna Levels ◽  
Fos Expression

We used quantitative reverse transcription (RT)/PCR to study the regulation of p75 mRNA and trkA mRNA expression in the developing sympathetic neurons of the mouse superior cervical sympathetic ganglion (SCG) in vivo and in vitro. At E13, the SCG contains proliferating cells that express many features of differentiated neurons. These immature neurons survived in culture without NGF, and NGF did not induce c-fos expression. Low levels of p75 and trkA mRNAs were expressed at this stage in vivo. There was no significant increase in the level of either trkA mRNA or p75 mRNA in E13 control cultures up to 72 h in vitro, and neither NGF nor depolarizing levels of K+ ions (40 mM KC1) affected the expression of trkA mRNA. In E14 cultures, NGF induced c-fos expression in 10-15% of the neurons and enhanced the survival of a similar percentage of neurons. The proportion of neurons responding to NGF increased with age, reaching 90% in E18 cultures. The in vivo level of trkA mRNA increased markedly from E14 onward, but in contrast to sensory neurons (in which p75 and trkA mRNA levels increase in parallel), the level of trkA mRNA initially increased far more rapidly than that of p75 mRNA. After E17, the level of p75 mRNA increased rapidly and approached that of trkA mRNA postnatally, but at no stage did this exceed the level of trkA mRNA. In E14 cultures, the level of trkA mRNA increased in the absence of neurotrophins or 40 mM KC1. The level of p75 mRNA in E14 cultures was enhanced by NGF but was unaffected by 40 mM KC1. Our findings show that NGF receptor expression during the earliest stages of sympathetic neuron development is not affected by depolarization but indicate that by an early developmental stage (between E13 and E14 in vivo), sympathetic neurons become specified to upregulate trkA mRNA in culture independently of added factors. In addition, our findings reveal several distinctive features of p75 mRNA and trkA mRNA expression in sympathetic neurons compared with sensory neurons and provide a plausible explanation for previously observed differences in the effects of a p75 null mutation on the response of sensory and sympathetic neurons during embryonic and postnatal development.

scholarly journals Olfactory Receptor Gene Regulation in Insects: Multiple Mechanisms for Singular Expression

2021 ◽  
Vol 15 ◽  
Author(s):  
Kaan Mika ◽  
Richard Benton
Keyword(s):  
Olfactory Receptor ◽  
Internal State ◽  
Receptor Gene ◽  
Expression Patterns ◽  
Olfactory Receptors ◽  
Regulatory Elements ◽  
Receptor Expression ◽  
Outstanding Question ◽  
The Brain ◽  
Large Repertoire

The singular expression of insect olfactory receptors in specific populations of olfactory sensory neurons is fundamental to the encoding of odors in patterns of neuronal activity in the brain. How a receptor gene is selected, from among a large repertoire in the genome, to be expressed in a particular neuron is an outstanding question. Focusing on Drosophila melanogaster, where most investigations have been performed, but incorporating recent insights from other insect species, we review the multilevel regulatory mechanisms of olfactory receptor expression. We discuss how cis-regulatory elements, trans-acting factors, chromatin modifications, and feedback pathways collaborate to activate and maintain expression of the chosen receptor (and to suppress others), highlighting similarities and differences with the mechanisms underlying singular receptor expression in mammals. We also consider the plasticity of receptor regulation in response to environmental cues and internal state during the lifetime of an individual, as well as the evolution of novel expression patterns over longer timescales. Finally, we describe the mechanisms and potential significance of examples of receptor co-expression.

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