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Receptors, Volume 2, Issue 2 (June 2023) – 3 articles

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6 pages, 2072 KiB  
Communication
Cycle Numbers of Cell Surface Recycling Receptors
by Dietmar Steverding
Receptors 2023, 2(2), 160-165; https://doi.org/10.3390/receptors2020010 - 6 Jun 2023
Cited by 2 | Viewed by 1586
Abstract
The cycle number (nc) of a recycling receptor is defined as the average number of round trips (cell surface–endosome–cell surface) the receptor can make before it is degraded. This characteristic parameter of recycling receptors can be easily determined from the [...] Read more.
The cycle number (nc) of a recycling receptor is defined as the average number of round trips (cell surface–endosome–cell surface) the receptor can make before it is degraded. This characteristic parameter of recycling receptors can be easily determined from the receptor’s half-life (t½, the time in which 50% of the receptor is degraded) and cycling time (Tc, the time a receptor needs to complete a round trip). Relationship analyses revealed that nc increases linearly with increasing t½ and decreases exponentially with increasing Tc. For commonly observed t½ and Tc values, it was calculated that recycling receptors have nc values of <300. In addition, it was found that recycling receptors in cancer cells have generally smaller nc values (<100), whereas recycling receptors in normal cells have larger nc values (>100). Based on this latter finding, the cycle number nc may be a useful criterion for distinguishing between cancer and normal cells. Full article
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12 pages, 4631 KiB  
Communication
Analysis of Cell–Cell Communication by Single-Nuclei RNA Sequencing Identifies AHR-Mediated Induction of NRG-ERBB Signaling
by Rance Nault, Giovan N. Cholico and Tim Zacharewski
Receptors 2023, 2(2), 148-159; https://doi.org/10.3390/receptors2020009 - 11 May 2023
Cited by 1 | Viewed by 2418
Abstract
Communication between cells is essential in maintaining homeostasis. The persistent disruption of cell–cell communication by environmental contaminants contributes to progressive disease and toxicity. In this study, single-nuclei RNA sequencing (snRNAseq) data was used to examine dose-dependent cell-specific changes in cell–cell communication associated with [...] Read more.
Communication between cells is essential in maintaining homeostasis. The persistent disruption of cell–cell communication by environmental contaminants contributes to progressive disease and toxicity. In this study, single-nuclei RNA sequencing (snRNAseq) data was used to examine dose-dependent cell-specific changes in cell–cell communication associated with the development of liver pathologies following the persistent activation of the aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Published hepatic snRNAseq data from male mice gavaged with sesame-oil vehicle or TCDD every 4 days for 28 days was used to assess the AHR-mediated disruption of ligand–receptor interactions. Analysis identified that portal fibroblasts and liver sinusoidal endothelial cells contributed the most ligand–receptor pairs at doses < 0.3μg/kg TCDD. Doses ≥ 0.3 μg/kg TCDD increased the putative intercellular communication between hepatocytes and hepatic stellate cells. In control livers, interactions primarily consisted of protease-activated receptor (PAR) signaling. TCDD treatment increased the number of active signaling pathways. Within hepatocytes, neuregulin signaling was induced, activating the NRG1–ERBB4 ligand axis, consistent with AHR genomic enrichment at dioxin response elements in a published chromatin immunoprecipitation sequencing (ChIP-seq) dataset, which suggested a direct regulation. Collectively, the results suggest that the disruption of cell signaling may play a central role in TCDD-elicited liver pathologies. Full article
(This article belongs to the Special Issue Selected Papers from the AHR Symposium 2022)
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21 pages, 3450 KiB  
Review
Molecular Characterization and Pharmacology of Melatonin Receptors in Animals
by Erika Cecon, Jean A. Boutin and Ralf Jockers
Receptors 2023, 2(2), 127-147; https://doi.org/10.3390/receptors2020008 - 14 Apr 2023
Cited by 6 | Viewed by 2922
Abstract
Melatonin, the hormone of darkness, is secreted in minute amounts during the night and is virtually undetectable during the day. Melatonin mainly acts on high-affinity G protein-coupled receptors. The present review will trace the path of the discovery of melatonin receptors from their [...] Read more.
Melatonin, the hormone of darkness, is secreted in minute amounts during the night and is virtually undetectable during the day. Melatonin mainly acts on high-affinity G protein-coupled receptors. The present review will trace the path of the discovery of melatonin receptors from their cloning, expression and purification to the development of recent radioactive and fluorescent tracers. We will then report on the state-of-the-art of melatonin receptor functional properties, including ligand bias and system bias due to receptor-associated proteins and receptor heteromers. Currently available antibodies raised against melatonin receptors will be critically reviewed here for the first time. The review will close with future perspectives in terms of the discovery of allosteric ligands and the in vivo validation of a range of melatonin receptor-associated signaling complexes to improve future drug development. Full article
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