scholarly journals Widespread Polymodal Chemosensory Receptor Expression in Drosophila Olfactory Neurons

2020 ◽  
Author(s):  
Darya Task ◽  
Chun-Chieh Lin ◽  
Ali Afify ◽  
Hongjie Li ◽  
Alina Vulpe ◽  
...  
Keyword(s):  
Antennal Lobe ◽  
Expression Patterns ◽  
Maxillary Palp ◽  
Receptor Expression ◽  
Olfactory Neurons ◽  
Olfactory Responses ◽  
Chemosensory Receptor ◽  
Endogenous Expression ◽  
Single Sensillum ◽  
And Function

ABSTRACTDrosophila olfactory neurons have long been thought to express only one chemosensory receptor modality. Using a new genetic knock-in strategy, we targeted the four co-receptors representing the chemosensory modes in Drosophila (Orco, Ir25a, Ir8a, Ir76b). Co-receptor knock-in expression patterns were verified as accurate representations of endogenous expression. We find extensive overlap in expression among the different co-receptors. As defined by innervation into antennal lobe glomeruli, Ir25a is broadly expressed in 88% of olfactory neuron classes and is co-expressed in 64% of Orco+ neuron classes, including all neuron classes in the maxillary palp. Orco, Ir8a, and Ir76b expression patterns are also expanded. Single sensillum recordings from Orco-expressing Ir25a mutant antennal and palpal neurons identify significant changes in olfactory responses. These results suggest polymodal expression and function of chemosensory receptors is common in olfactory neurons. We present a new map of the olfactory system reflecting this polymodal expression.

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.

scholarly journals Transmitter Co-Expression Reveals Key Organizational Principles of Local Interneuron Heterogeneity in the Olfactory System

2017 ◽  
Author(s):  
Kristyn M. Lizbinski ◽  
Gary F. Marsat ◽  
Andrew M. Dacks
Keyword(s):  
Antennal Lobe ◽  
Expression Patterns ◽  
Receptor Expression ◽  
Projection Neurons ◽  
Local Interneuron ◽  
Local Interneurons ◽  
Receptor Neurons ◽  
Random Probability ◽  
Organizational Principles ◽  
Organizing Principles

AbstractHeterogeneity of individual neurons within a population expands the computational power of the entire neural network. However, the organizing principles that support heterogeneity within a neuronal class are often poorly understood. Here, we focus on a highly heterogeneous population of local interneurons whose traits co-vary seemingly at random. We asked if local interneurons (LNs) in the antennal lobe (AL) of Manduca sexta express fixed, predictable combinations of neurotransmitters, or if transmitter co-expression can be explained by random probability. We systematically determined the co-expression of neuropeptides and GABA by LNs and found variable patterns of co-expression for all neuropeptides, except for tachykininergic LNs which exhibited highly stereotyped co-expression on a neuron-by-neuron basis. To test if observed patterns of co-expression were random, we used a computational model and found that the probabilities of transmitter co-expression cannot be explained by independent expression of each transmitter. We also determined that setting a single rule in the model, while leaving the rest of the co-expression up to random probability, allowed the model to replicate the overall heterogeneity of transmitter co-expression across antennal lobe LNs. This implies that certain co-expression relationships contribute to the ground plan of the AL, but that otherwise, transmitter expression amongst LNs may be random, allowing heterogeneous co-expression patterns to emerge. Furthermore, neuropeptide receptor expression suggests that peptidergic signaling from LNs may simultaneously target olfactory receptor neurons, LNs and projection neurons, and thus the effects of different peptides do not segregate based on principal AL cell type. Our data suggest that while specific constraints may partially shape transmitter co-expression in LNs, a large amount of flexibility on a neuron-by-neuron basis produces heterogeneous network parameters.

Role of the 807 C/T Polymorphism of the α2 Gene in Platelet GP Ia Collagen Receptor Expression and Function

1999 ◽  
Vol 81 (06) ◽  
pp. 951-956 ◽  
Author(s):  
J. Corral ◽  
R. González-Conejero ◽  
J. Rivera ◽  
F. Ortuño ◽  
P. Aparicio ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Cell Types ◽  
Receptor Expression ◽  
Case Control Studies ◽  
Platelet Surface ◽  
Vitro Analysis ◽  
And Function ◽  
In Vitro Analysis

SummaryThe variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by “in vitro” analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.

P2 receptor expression signaling and function in osteoclasts

10.2741/s214 ◽  
2011 ◽  
Vol S3 (3) ◽  
pp. 1101-1118
Author(s):  
S. Jeffrey Dixon
Keyword(s):  
Receptor Expression ◽  
P2 Receptor ◽  
And Function

scholarly journals Differential Regulation of Gonadotropins as Revealed by Transcriptomes of Distinct LH and FSH Cells of Fish Pituitary

2021 ◽  
Vol 22 (12) ◽  
pp. 6478
Author(s):  
Lian Hollander-Cohen ◽  
Matan Golan ◽  
Berta Levavi-Sivan
Keyword(s):  
Follicle Stimulating Hormone ◽  
Differential Regulation ◽  
Receptor Expression ◽  
Hormone Regulation ◽  
Fish Reproduction ◽  
Cell Type ◽  
Conserved Genes ◽  
Transgenic Tilapia ◽  
And Function ◽  
Direct Regulation

From mammals to fish, reproduction is driven by luteinizing hormone (LH) and follicle-stimulating hormone (FSH) temporally secreted from the pituitary gland. Teleost fish are an excellent model for addressing the unique regulation and function of each gonadotropin cell since, unlike mammals, they synthesize and secrete LH and FSH from distinct cells. Only very distant vertebrate classes (such as fish and birds) demonstrate the mono-hormonal strategy, suggesting a potential convergent evolution. Cell-specific transcriptome analysis of double-labeled transgenic tilapia expressing GFP and RFP in LH or FSH cells, respectively, yielded genes specifically enriched in each cell type, revealing differences in hormone regulation, receptor expression, cell signaling, and electrical properties. Each cell type expresses a unique GPCR signature that reveals the direct regulation of metabolic and homeostatic hormones. Comparing these novel transcriptomes to that of rat gonadotrophs revealed conserved genes that might specifically contribute to each gonadotropin activity in mammals, suggesting conserved mechanisms controlling the differential regulation of gonadotropins in vertebrates.

scholarly journals Integrated molecular characterisation of endometrioid ovarian carcinoma identifies opportunities for stratification

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Robert L. Hollis ◽  
Barbara Stanley ◽  
John P. Thomson ◽  
Michael Churchman ◽  
Ian Croy ◽  
...  
Keyword(s):  
High Risk ◽  
Ovarian Carcinoma ◽  
Expression Patterns ◽  
Parp Inhibitors ◽  
Receptor Expression ◽  
Cancer Type ◽  
Sequencing Data ◽  
Molecular Features ◽  
Endometrioid Ovarian Carcinoma ◽  
Molecular Landscape

AbstractEndometrioid ovarian carcinoma (EnOC) is an under-investigated ovarian cancer type. Recent studies have described disease subtypes defined by genomics and hormone receptor expression patterns; here, we determine the relationship between these subtyping layers to define the molecular landscape of EnOC with high granularity and identify therapeutic vulnerabilities in high-risk cases. Whole exome sequencing data were integrated with progesterone and oestrogen receptor (PR and ER) expression-defined subtypes in 90 EnOC cases following robust pathological assessment, revealing dominant clinical and molecular features in the resulting integrated subtypes. We demonstrate significant correlation between subtyping approaches: PR-high (PR + /ER + , PR + /ER−) cases were predominantly CTNNB1-mutant (73.2% vs 18.4%, P < 0.001), while PR-low (PR−/ER + , PR−/ER−) cases displayed higher TP53 mutation frequency (38.8% vs 7.3%, P = 0.001), greater genomic complexity (P = 0.007) and more frequent copy number alterations (P = 0.001). PR-high EnOC patients experience favourable disease-specific survival independent of clinicopathological and genomic features (HR = 0.16, 95% CI 0.04–0.71). TP53 mutation further delineates the outcome of patients with PR-low tumours (HR = 2.56, 95% CI 1.14–5.75). A simple, routinely applicable, classification algorithm utilising immunohistochemistry for PR and p53 recapitulated these subtypes and their survival profiles. The genomic profile of high-risk EnOC subtypes suggests that inhibitors of the MAPK and PI3K-AKT pathways, alongside PARP inhibitors, represent promising candidate agents for improving patient survival. Patients with PR-low TP53-mutant EnOC have the greatest unmet clinical need, while PR-high tumours—which are typically CTNNB1-mutant and TP53 wild-type—experience excellent survival and may represent candidates for trials investigating de-escalation of adjuvant chemotherapy to agents such as endocrine therapy.

scholarly journals Efficient IL-2R signaling differentially affects the stability, function, and composition of the regulatory T-cell pool

2021 ◽  
Author(s):  
Marc Permanyer ◽  
Berislav Bošnjak ◽  
Silke Glage ◽  
Michaela Friedrichsen ◽  
Stefan Floess ◽  
...  
Keyword(s):  
T Cell ◽  
Treg Cell ◽  
Cell Function ◽  
Interleukin 2 ◽  
Foxp3 Expression ◽  
Treg Cells ◽  
Receptor Expression ◽  
Spontaneous Mutant ◽  
Cell Pool ◽  
And Function

AbstractSignaling via interleukin-2 receptor (IL-2R) is a requisite for regulatory T (Treg) cell identity and function. However, it is not completely understood to what degree IL-2R signaling is required for Treg cell homeostasis, lineage stability and function in both resting and inflammatory conditions. Here, we characterized a spontaneous mutant mouse strain endowed with a hypomorphic Tyr129His variant of CD25, the α-chain of IL-2R, which resulted in diminished receptor expression and reduced IL-2R signaling. Under noninflammatory conditions, Cd25Y129H mice harbored substantially lower numbers of peripheral Treg cells with stable Foxp3 expression that prevented the development of spontaneous autoimmune disease. In contrast, Cd25Y129H Treg cells failed to efficiently induce immune suppression and lost lineage commitment in a T-cell transfer colitis model, indicating that unimpaired IL-2R signaling is critical for Treg cell function in inflammatory environments. Moreover, single-cell RNA sequencing of Treg cells revealed that impaired IL-2R signaling profoundly affected the balance of central and effector Treg cell subsets. Thus, partial loss of IL-2R signaling differentially interferes with the maintenance, heterogeneity, and suppressive function of the Treg cell pool.

scholarly journals Microglial Function and Regulation during Development, Homeostasis and Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 957
Author(s):  
Brad T. Casali ◽  
Erin G. Reed-Geaghan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Cells ◽  
Expression Patterns ◽  
Brain Parenchyma ◽  
Primary Role ◽  
And Function ◽  
Inflammatory Milieu ◽  
The Brain ◽  
Homeostatic State

Microglia are the resident immune cells of the brain, deriving from yolk sac progenitors that populate the brain parenchyma during development. During development and homeostasis, microglia play critical roles in synaptogenesis and synaptic plasticity, in addition to their primary role as immune sentinels. In aging and neurodegenerative diseases generally, and Alzheimer’s disease (AD) specifically, microglial function is altered in ways that significantly diverge from their homeostatic state, inducing a more detrimental inflammatory environment. In this review, we discuss the receptors, signaling, regulation and gene expression patterns of microglia that mediate their phenotype and function contributing to the inflammatory milieu of the AD brain, as well as strategies that target microglia to ameliorate the onset, progression and symptoms of AD.

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