Using multiplexed single-cell transcriptomics, we analyze human neural precursor cells (hNPCs) from sporadic

Role of G Protein-Coupled Receptors in Hepatic Stellate Cells and Approaches to Anti-Fibrotic Treatment G protein-coupled receptors (GPCRs) are cell surface receptors that mediate the function of a great variety However, our knowledge of how GPCRs regulate liver metabolism and fibrosis in the different cell types In particular, a better understanding of the role of GPCRs in hepatic stellate cells (HSCs), the primary cells that regulate liver fibrosis, may lead to the development of drugs that can improve hepatic fibrosis

August 2022 G protein-coupled receptor kinase type 2 and β-arrestin2: Key players in immune cell functions β-arrestin2 are key integrated signaling nodes in various biological processes, and both of them regulate cell proliferation and promote cell invasion and migration. This review summarizes the roles of GRK2/β-arrestin2 in immune cell function and focuses on the pathological

possesses both immune and vascular privilege, in part due to its unique repertoire of resident immune cells Corneal nerves produce various neuropeptides that have a wide range of functions on immune cells.

PLC-IP3-ORAI pathway participates in the activation of the MRGPRB2 receptor in mouse peritoneal mast cells "A novel mast cell-specific G-protein-coupled receptor (GPCR), known as Mas-related G protein-coupled indicated the involvement of the PLC-IP3-ORAI signaling pathway and CACCS in MRGPRB2-mediated mast cell

Join us for the first virtual cafe talk to hear about the amazing work that Dr. Brian Arey is doing. https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe

various chemokine/chemokine receptor axes in trafficking and oriented locomotion of mesenchymal stem cells Application of mesenchymal stem cells (MSCs) as an emerging approach was recruited forthe treatment of Chemokines are low molecular weight proteins that their functional activities are achieved by binding to the cell Chemokine/chemokine receptor axes play a pivotal role in the recruitment and oriented trafficking of immune cells of MS patients via expression of various chemokine receptors in response to chemokines expressed by cells

Through gene expression analysis in immune and gastrointestinal cells, we show that these isoforms emerge Additionally, we employed optical assays in living cells to thoroughly profile both GPR35 isoforms for

and Clinical Pharmacology GPCR Jobs NEW GPCR Molecular Pharmacologist Scientist - Biology Scientist I Cell in Molecular Pharmacology - The Hauser Group Postdoctoral Scholar – iPSC in cardiac and endothelial cell Long-Term Outcomes in Patients With Multiple Myeloma and Lymphoma Undergoing Chimeric Antigen Receptor T-Cell RNAi library screening reveals Gβ1, Casein Kinase 2 and ICAP-1 as novel regulators of LFA-1-mediated T cell polarity and migration Methods & Updates in GPCR Research Calcineurin-fusion facilitates cryo-EM structure

Treatment of cells with YM failed to inhibit signaling by these PM-restricted αqQ209L.

Divergent roles for the gut intraepithelial lymphocyte GLP-1R in control of metabolism, microbiota, and T cell-induced Here, we show that the gut IEL GLP-1 receptor (GLP-1R) is not required for enteroendocrine L cell GLP anti-inflammatory actions of GLP-1RAs require the gut IEL GLP-1R to selectively restrain local and systemic T cell-induced are mediated by the suppression of gut IEL effector functions linked to the dampening of proximal T cell These data reposition key roles of the L cell-gut IEL GLP-1R axis, revealing mechanisms linking GLP-1R

Inhibition of autophagy by 3-methyladenine or interference of ATG5 or ATG7 attenuated HBx-induced cell

the Classified GPCR News from January 29th to February 4th, 2024 Adhesion GPCRs CELSR1, a core planar cell polarity protein, features a weakly adhesive and flexible cadherin ectodomain GPCR Activation and Signaling

September 2022 "The activation of phospholipase C (PLC) is thought to have a key role in the cardiomyocyte response to several different hypertrophic agents such as norepinephrine, angiotensin II and endothelin-1. PLC activity results in the generation of diacylglycerol and inositol trisphosphate, which are downstream signal transducers for the expression of fetal genes, increased protein synthesis, and subsequent cardiomyocyte growth. In this article, we describe the signal transduction elements that regulate PLC gene expression. The discussion is focused on the norepinephrine- α1-adrenoceptor signaling pathway and downstream signaling processes that mediate an upregulation of PLC isozyme gene expression. Evidence is also indicated to demonstrate that PLC activities self-regulate the expression of PLC isozymes with the suggestion that PLC activities may be part of a coordinated signaling process for the perpetuation of cardiac hypertrophy. Accordingly, from the information provided, it is plausible that specific PLC isozymes could be targeted for the mitigation of cardiac hypertrophy." Read more at the source #DrGPCR #GPCR #IndustryNews

Here, we examine how HH controls SMO subcellular localization and activity in a polarized epithelium of HH, the second effect of FU leads to the local enrichment of SMO in the most basal domain of the cell

October 2022 "Visual phototransduction is the most extensively studied G protein-coupled receptor (GPCR) signaling pathway because of its quantifiable stimulus, non-redundancy of genes, and immense importance in vision. We summarize recent discoveries that have advanced our understanding of rod outer segment (ROS) morphology and the pathological basis of retinal diseases. We have combined recently published cryo-electron tomography (cryo-ET) data on the ROS with structural knowledge on individual proteins to define the precise spatial limitations under which phototransduction occurs. Although hypothetical, the reconstruction of the rod phototransduction system highlights the potential roles of phosphodiesterase 6 (PDE6) and guanylate cyclases (GCs) in maintaining the spacing between ROS discs, suggesting a plausible mechanism by which intrinsic optical signals are generated in the retina." Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Regulation of pulmonary surfactant by the adhesion GPCR GPR116/ADGRF5 requires a tethered agonist-mediated activation mechanism "The mechanistic details of the tethered agonist mode of activation for the adhesion GPCR ADGRF5/GPR116 have not been completely deciphered. We set out to investigate the physiological importance of autocatalytic cleavage upstream of the agonistic peptide sequence, an event necessary for NTF displacement and subsequent receptor activation. To examine this hypothesis, we characterized tethered agonist-mediated activation of GPR116 in vitro and in vivo. A knock-in mouse expressing a non-cleavable GPR116 mutant phenocopies the pulmonary phenotype of GPR116 knock-out mice, demonstrating that tethered agonist-mediated receptor activation is indispensable for function in vivo. Using site-directed mutagenesis and species-swapping approaches, we identified key conserved amino acids for GPR116 activation in the tethered agonist sequence and in extracellular loops 2/3 (ECL2/3). We further highlight residues in transmembrane 7 (TM7) that mediate stronger signaling in mouse versus human GPR116 and recapitulate these findings in a model supporting tethered agonist:ECL2 interactions for GPR116 activation." Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "We describe production of the human A2A adenosine receptor (A2AAR), a class A G protein-coupled receptor (GPCR) for 19F-NMR and single-molecule fluorescence (SMF) spectroscopy. We explain in detail steps shared between the two sample preparation strategies, including expression and isolation of A2AAR and assembly of A2AAR in lipid nanodiscs and procedures for incorporation of either 19F-NMR or fluorescence probes. Protocols for SMF experiments include sample setup, data acquisition, data processing, and error analysis. For complete details on the use and execution of this protocol, please refer to Wei et al. (2022) and Sušac et al. (2018)." Read more at the source #DrGPCR #GPCR #IndustryNews

the efficacy of seven agonists to induce G protein, G protein-coupled receptor kinase 2 (GRK2), as well

September 2022 "The follicle-stimulating hormone receptor (FSHR) belongs to the glycoprotein hormone receptors, a subfamily of G-protein-coupled receptors (GPCRs). FSHR is involved in reproductive processes such as gonadal development and maturation. Structurally, the extensive extracellular domain, which contains the hormone-binding site and is linked to the transmembrane domain by the hinge region (HR), is characteristic for these receptors. How this HR is involved in hormone binding and signal transduction is still an open question. We combined in vitro and in situ chemical crosslinking, disulfide pattern analysis, and mutation data with molecular modeling to generate experimentally driven full-length models. These models provide insights into the interface, important side-chain interactions, and activation mechanism. The interface indicates a strong involvement of the connecting loop. A major rearrangement of the HR seems implausible due to the tight arrangement and fixation by disulfide bonds. The models are expected to allow for testable hypotheses about signal transduction and drug development for GPHRs." Read more at the source #DrGPCR #GPCR #IndustryNews

Characterization of a new WHIM syndrome mutant reveals mechanistic differences in regulation of the chemokine receptor CXCR4 WHIM syndrome is a rare immunodeficiency disorder that is characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. While several gain-of-function mutations that lead to C-terminal truncations, frame shifts and point mutations in the chemokine receptor CXCR4 have been identified in WHIM syndrome patients, the functional effect of these mutations are not fully understood. Here, we report on a new WHIM syndrome mutation that results in a frame shift within the codon for Ser339 (S339fs5) and compare the properties of S339fs5 with wild type CXCR4 and a previously identified WHIM syndrome mutant, R334X. The S339fs5 and R334X mutants exhibited significantly increased signaling compared to wild type CXCR4 including agonist-promoted calcium flux and extracellular signal-regulated kinase activation. This increase is at least partially due to a significant decrease in agonist-promoted phosphorylation, β-arrestin binding, and endocytosis of S339fs5 and R334X compared to wild type CXCR4. Interestingly, there were also significant differences in receptor degradation, with S339fs5 having a very high basal level of degradation compared to that of R334X and wild type CXCR4. In contrast to wild type CXCR4, both R334X and S339fs5 were largely insensitive to CXCL12-promoted degradation. Moreover, while basal and agonist-promoted degradation of wild type CXCR4 was effectively inhibited by the CXCR4 antagonist TE-14016, this had no effect on the degradation of the WHIM mutants. Taken together, these studies identify a new WHIM syndrome mutant, CXCR4-S339fs5, that promotes enhanced signaling, reduced phosphorylation, β-arrestin binding and endocytosis, and a very high basal rate of degradation that is not protected by antagonist treatment. Read full article

August 2022 "GPCRs in Medicinal Chemistry Event 8th RSC / SCI symposium on GPCRs in Medicinal Chemistry Dates Wednesday-Friday, 5th-7th October 2022 Place Evotec Campus Levi-Montalcini, Verona, Italy Downloads and Links Registration closing dates: 6th September – registration against invoice (bank transfers): Tuesday, 6th September 30th September – online registration (card payments)" Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "WELCOME 4GPCRnet meeting bringing together four of the biggest GPCR networks in Europe for a joint meeting in Leipzig. Four of the biggest European networks on GPCR research (COST Actions Adher’n Rise and ERNEST plus DFG-funded SFB1423 and FOR2372) have joined forces to organize an international meeting, which will take place from 26th-29th September 2022 in the beautiful city of Leipzig in Germany. We aim to connect renowned international experts of the field with early career ‘rising stars’. The event will take place in the heart of Leipzig, which offers a colorful mixture of culture and vivid social life." Read more at the source #DrGPCR #GPCR #IndustryNews

Discovery on Target (DOT) highlights advances in current and emerging “hot” targets and technologies, as well

August 2022 RAB-Symposium - Regulatory Autoantibodies Targeting GPCRs. September 15-16, 2022. Lübeck, Germany. Hybrid meeting. "Dear Sir or Madam, dear Colleagues, It gives me great pleasure to announce the fourth hybrid symposium on regulatory autoantibodies targeting G-protein-coupled receptors (GPCRs) in Lübeck. GPCRs are involved in a variety of physiological and pathophysiological processes. So far, numerous therapeutics targeting GPCRs have been developed, with a focus on small molecules and monoclonal antibodies for the treatment of cancer, infections, metabolic disorders or inflammatory diseases. Recently, functional autoantibodies targeting GPCRs have been associated with various disease-specific manifestations, highlighting a potential new area for therapeutic intervention. Therefore, the aim of this symposium is to bring together the current knowledge on the role of autoantibodies targeting GPCRs in various diseases, such as cardiovascular diseases, renal diseases, autoimmune diseases such as systemic sclerosis or systemic lupus erythematosus. In addition, one aim is to bring together the mode of action of autoantibodies in immune regulation and pathogenesis." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "We are happy to announce you our 2nd IRN i-GPCRnet meeting that will be held at the University of Wurzburg (Germany) from september 30th to october 1rst." Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Bell-Evans model and steered molecular dynamics in uncovering the dissociation kinetics optimized approach of combining the data derived from steered molecular dynamics simulations and the Bell-Evans

medium-chain free fatty acid receptor GPR84 is a G protein-coupled receptor primarily expressed in myeloid cells macrophages through enhancing NLRP3 inflammasome activation, while the loss of GPR84 prevents the M1 polarization CLH536, a novel GPR84 antagonist discovered by us, suppresses colitis by reducing the polarization and These results define a unique role of GPR84 in innate immune cells and intestinal inflammation, and suggest