scholarly journals Functional Characterization of Olfactory Receptors in the Thyroid Gland

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniel Weidinger ◽  
Nikolina Jovancevic ◽  
Denise Zwanziger ◽  
Sarah Theurer ◽  
Judith Hönes ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Olfactory Receptors ◽  
Malignant Cell ◽  
Human Thyroid ◽  
Downstream Signaling ◽  
Cascade Analysis ◽  
Proliferation And Invasion ◽  
Specific Ligand ◽  
Stimulation Of

Olfactory receptors (ORs) are almost ubiquitously expressed in the human body. However, information about their functions in these tissues is lacking. To date, no functional characterization of expressed ORs in the human thyroid has been performed. In this study, we detected and compared the expression of OR2H2 and OR2W3 in healthy and malignant cell lines and their corresponding tissues, respectively. We demonstrated that stimulation of ORs by their specific ligand resulted in a transient increase in intracellular calcium and cAMP concentrations. In the case of OR2H2, the downstream signaling cascade analysis revealed that adenylate cyclase (AC) and phosphoinositide phospholipase C (PLC) were involved. Furthermore, OR2H2 and OR2W3 activation affected migration, proliferation, and invasion. These are the first insights that ORs influence physiology-relevant processes in the healthy and malignant thyroid.

scholarly journals Functional Characterization of Two Human Olfactory Receptors Expressed in the Baculovirus Sf9 Insect Cell System

2005 ◽  
Vol 30 (3) ◽  
pp. 195-207 ◽  
Author(s):  
V. Matarazzo ◽  
O. Clot-Faybesse ◽  
B. Marcet ◽  
G. Guiraudie-Capraz ◽  
B. Atanasova ◽  
...  
Keyword(s):  
Insect Cell ◽  
Functional Characterization ◽  
Olfactory Receptors ◽  
Cell System

scholarly journals Functional Characterization of Muscarinic Receptors in Human Schwann Cells

2020 ◽  
Vol 21 (18) ◽  
pp. 6666
Author(s):  
Roberta Piovesana ◽  
Alessandro Faroni ◽  
Ada Maria Tata ◽  
Adam J. Reid
Keyword(s):  
Cell Proliferation ◽  
Schwann Cells ◽  
Muscarinic Receptor ◽  
Muscarinic Receptors ◽  
Functional Characterization ◽  
Receptor Subtypes ◽  
Muscarinic Receptor Subtypes ◽  
Selective Stimulation ◽  
Stimulation Of

Functional characterization of muscarinic cholinergic receptors in myelinating glial cells has been well described both in central and peripheral nervous system. Rat Schwann cells (SCs) express different muscarinic receptor subtypes with the prevalence of the M2 subtype. The selective stimulation of this receptor subtype inhibits SC proliferation, improving their differentiation towards myelinating phenotype. In this work, we describe for the first time that human SCs are cholinoceptive as they express several muscarinic receptor subtypes and, as for rat SCs, M2 receptor is one of the most abundant. Human SCs, isolated from adult nerves, were cultured in vitro and stimulated with M2 muscarinic agonist arecaidine propargyl ester (APE). Similarly to that observed in rat, M2 receptor activation causes a decreased cell proliferation and promotes SC differentiation as suggested by increased Egr2 expression with an improved spindle-like shape cell morphology. Conversely, the non-selective stimulation of muscarinic receptors appears to promote cell proliferation with a reduction of SC average cell diameter. The data obtained demonstrate that human SCs are cholinoceptive and that human cultured SCs may represent an interesting tool to understand their physiology and increase the knowledge on how the cholinergic stimulation may contribute to address human SC development in normal and pathological conditions.

scholarly journals The infantile myofibromatosis NOTCH3 L1519P mutation leads to hyperactivated ligand-independent Notch signaling and increased PDGFRB expression

2021 ◽  
Vol 14 (2) ◽  
pp. dmm046300
Author(s):  
Dan Wu ◽  
Sailan Wang ◽  
Daniel V. Oliveira ◽  
Francesca Del Gaudio ◽  
Michael Vanlandewijck ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Extracellular Domain ◽  
Infantile Myofibromatosis ◽  
Independent Manner ◽  
Functional Link ◽  
Downstream Signaling ◽  
Chloroquine Treatment ◽  
Notch3 Mutation ◽  
The Relationship

ABSTRACTInfantile myofibromatosis (IMF) is a benign tumor form characterized by the development of nonmetastatic tumors in skin, bone, muscle and sometimes viscera. Autosomal-dominant forms of IMF are caused by mutations in the PDGFRB gene, but a family carrying a L1519P mutation in the NOTCH3 gene has also recently been identified. In this study, we address the molecular consequences of the NOTCH3L1519P mutation and the relationship between Notch and PDGFRB signaling in IMF. The NOTCH3L1519P receptor generates enhanced downstream signaling in a ligand-independent manner. Despite the enhanced signaling, the NOTCH3L1519P receptor is absent from the cell surface and instead accumulates in the endoplasmic reticulum. Furthermore, the localization of the NOTCH3L1519P receptor in the bipartite, heterodimeric state is altered, combined with avid secretion of the mutated extracellular domain from the cell. Chloroquine treatment strongly reduces the amount of secreted NOTCH3L1519P extracellular domain and decreases signaling. Finally, NOTCH3L1519P upregulates PDGFRB expression in fibroblasts, supporting a functional link between Notch and PDGF dysregulation in IMF. Collectively, our data define a NOTCH3–PDGFRB axis in IMF, in which an IMF-mutated NOTCH3 receptor elevates PDGFRB expression. The functional characterization of a ligand-independent gain-of-function NOTCH3 mutation is important for Notch therapy considerations for IMF, including strategies aimed at altering lysosome function.

scholarly journals Functional characterization of odor responses and gene expression changes in olfactory co-receptor mutants in Drosophila

2021 ◽  
Author(s):  
Alina Vulpe ◽  
Pratyajit Mohapatra ◽  
Karen Menuz
Keyword(s):  
Gene Expression ◽  
Olfactory System ◽  
Transcriptional Profiling ◽  
Functional Characterization ◽  
Olfactory Receptors ◽  
Odorant Receptors ◽  
Olfactory Neurons ◽  
Individual Odor ◽  
Receptor Neurons

Two large families of olfactory receptors, the Odorant Receptors (ORs) and the Ionotropic Receptors (IRs), mediate responses to most odors in the insect olfactory system. Individual odor binding tuning OR receptors are expressed by olfactory neurons in basiconic and trichoid sensilla and require the co-receptor Orco to function. The situation for IRs is more complex. Different tuning IR receptors are expressed by olfactory neurons in coeloconic sensilla and rely on either the Ir25a or Ir8a co-receptors; some evidence suggests that Ir76b may also act as a co-receptor, but its function has not been systematically examined. This is particularly important as recent data indicate that nearly all coeloconic olfactory neurons co-express Ir25a, Ir8a, and Ir76b. Here, we report the effects of Drosophila olfactory co-receptor mutants on odor detection by coeloconic olfactory neurons and determine their broader impact on gene expression through RNASeq analysis. We demonstrate that Ir76b and Ir25a function together in all amine-sensing olfactory receptor neurons. In most neurons, loss of either co-receptor abolishes amine responses, whereas in ac1 sensilla, amine responses persist in the absence of Ir76b or Ir25a, but are lost in a double-mutant. Such responses do not require Ir8a. Conversely, acid-sensing ORNs require Ir8a, but not Ir76b or Ir25a. Using antennal transcriptional profiling, we find that the expression of acid-sensing IR receptors is significantly reduced in Ir8a mutants, but is unaffected by the loss of Ir25a or Ir76b. Similarly, select OR tuning receptors are also downregulated in Orco2 mutants. In contrast, expression of amine-sensing IR receptors is mostly unchanged in Ir25a and Ir76b mutants. Together, our data reveal new aspects of co-receptor function in the olfactory system.

scholarly journals Mixture interactions at mammalian olfactory receptors are dependent on the cellular environment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elizabeth A. Corey ◽  
Sergei Zolotukhin ◽  
Barry W. Ache ◽  
Kirill Ukhanov
Keyword(s):  
Sensory Neurons ◽  
Functional Characterization ◽  
Olfactory Receptors ◽  
Response Dynamics ◽  
Cellular Environment ◽  
Odor Exposure ◽  
Mixture Interactions

AbstractFunctional characterization of mammalian olfactory receptors (ORs) remains a major challenge to ultimately understanding the olfactory code. Here, we compare the responses of the mouse Olfr73 ectopically expressed in olfactory sensory neurons using AAV gene delivery in vivo and expressed in vitro in cell culture. The response dynamics and concentration-dependence of agonists for the ectopically expressed Olfr73 were similar to those reported for the endogenous Olfr73, however the antagonism previously reported between its cognate agonist and several antagonists was not replicated in vivo. Expressing the OR in vitro reproduced the antagonism reported for short odor pulses, but not for prolonged odor exposure. Our findings suggest that both the cellular environment and the stimulus dynamics shape the functionality of Olfr73 and argue that characterizing ORs in ‘native’ conditions, rather than in vitro, provides a more relevant understanding of ligand-OR interactions.

scholarly journals Functional Characterization of Human Thyroid Tissue with Immunohistochemistry

Thyroid ◽  
2007 ◽  
Vol 17 (3) ◽  
pp. 203-211 ◽  
Author(s):  
Antongiulio Faggiano ◽  
Bernard Caillou ◽  
Ludovic Lacroix ◽  
Monique Talbot ◽  
Sebastiano Filetti ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Thyroid Tissue ◽  
Human Thyroid ◽  
Human Thyroid Tissue

scholarly journals Mixture Interactions at Mammalian Olfactory Receptors are Dependent on the Cellular Environment

2020 ◽  
Author(s):  
Elizabeth Corey ◽  
Sergei Zolotukhin ◽  
Barry Ache ◽  
Kirill Ukhanov
Keyword(s):  
Sensory Neurons ◽  
Functional Characterization ◽  
Olfactory Receptors ◽  
Response Dynamics ◽  
Complete Understanding ◽  
Cellular Environment ◽  
Mixture Interactions

Abstract Functional characterization of mammalian olfactory receptors (ORs) remains a major challenge to ultimately understanding the olfactory code. Here, we compare the responses of the mouse Olfr73 ectopically expressed in olfactory sensory neurons using AAV gene delivery in vivo and expressed in vitro in cell culture. The response dynamics and concentration-dependence of agonists for the ectopically expressed Olfr73 were similar to those reported for the endogenous Olfr73, but the receptor failed to mediate the antagonism between its cognate agonist and several antagonists reported for the OR expressed in vitro. Expressing the OR in vitro under the same conditions of stimulation retained the reported antagonism, but it was dependent on the duration of stimulation. Our findings suggest that both the cellular environment and the stimulus dynamics shape the functionality of Olfr73 and argue that characterizing ORs in ‘native’ conditions provides the most complete understanding of ligand-OR interactions.

Sign in / Sign up

Export Citation Format

Share Document