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

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

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

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

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

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

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 "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 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

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

October 2022 "Perturbation of the endocannabinoid system can have profound effects on immune function Microglia are one of few cell types with a self-contained endocannabinoid system and are positioned at the interface between the immune system and the central nervous system.

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

S1P5 is predominantly expressed in nervous and immune systems, regulating the egress of natural killer cells from lymph nodes and playing a role in immune and neurodegenerative disorders, as well as carcinogenesis

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

March 2022 " Geneva, Switzerland, March 7, 2022 – Addex Therapeutics (SIX: ADXN, Nasdaq: ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based drug discovery and development, announced today that it will issue its full-year 2021 financial results on Thursday, March 10, 2022. Tim Dyer , CEO, Roger Mills , CMO and Robert Lütjens , Head of Discovery Biology, will provide a business update and review its pipeline during a teleconference and webcast for investors, analysts and media at 16:00 CET (15:00 GMT / 10:00 EST / 07:00 PST) the same day. " Read more at the source #DrGPCR #GPCR #IndustryNews

with their receptors, are involved in various biologic processes and regulation of a wide range of immune that the ligation of SDF-1 to CXCR4 initiates several intracellular signaling pathways, regulating cell proliferation, survival, chemotaxis, migration, angiogenesis, adhesion, as well as bone marrow (BM)- resident cells homing and mobilization. Additionally, CXCR4 is expressed by tumor cells in blood malignancies and solid tumors."

September 2022 "T cells are master regulators of the immune response tuning, among others, B cells, macrophages and NK cells. To exert their functions requiring high sensibility and specificity, T cells need to integrate different of the cytoskeleton and lipid microdomains in controlling signalling compartmentalization during T cell Here, we discuss mechanisms responsible for signalling amplification and compartmentalization in T cell

Kevin Wright on his new position as Director of Targeted and Immuno-oncology at GPCR Therapeutics, our cytarabine, G-CSF, and mitoxantrone in untreated AML miR-19a may function as a biomarker of oral squamous cell the signaling pathway of miR-19a/GRK6/GPCRs/PKC in a Chinese population Identification of S1PR4 as an immune microenvironment in melanoma Methods & Updates in GPCR Research Genetic atlas of hygro-and thermosensory cells Technician Senior Research Associate, In Vitro Pharmacology - Crinetics Pharmaceuticals Postdoc In Cell

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

The molecular mechanisms N. meningitidis employ to manipulate the immune system, translocate the mucosal Both groups of metabolites suppress anti-inflammatory interleukin-10 signaling in human macrophage cell they also suppress the pro-inflammatory interleukin-17A+ population in TH 17-differentiated CD4+ T cells

are ancient large DNA viruses that have exploited gene capture as part of their strategy to escape immune surveillance, promote virus spreading, or reprogram host cells to benefit their survival.

placentation, uteroplacental malperfusion, oxidative stress, endoplasmic reticulum stress, dysregulated immune tolerance, vascular inflammation and endothelial cell dysfunction.

comprising international leaders in GPCRs pharmacology, immunology, drug discovery and development for auto-immune

Front Cell Dev Biol, 2021. 9: p. 611443. 3.      ., Revealing the Activity of Trimeric G-proteins in Live Cells with a Versatile Biosensor Design.  Cell, 2020. 182(3): p. 770-785.e16. 4.      Galés, C., et al., Real-time monitoring of receptor and G-protein interactions in living cells.  Goyet, E., et al., Fast and high resolution single-cell BRET imaging. 

phosphoinositide 3-kinase (PI3K) pathway, which plays fundamental roles in growth, metabolism, and immunity PI3Kγ is a critical component in multiple immune signaling processes and is dependent on activation by Ras and G protein-coupled receptors (GPCRs) to mediate its cellular roles.

GPCRs in Oncology and Immunology The GPCR-Gαs-PKA signaling axis promotes T cell dysfunction and cancer induces IFN-γ but suppresses IL-2 production by inhibiting activation of pAKT pathways in primary T cells partner on GPCR-targeting antibodies GPCR Inhibition With ICB May Be Needed to Reactivate Antitumor Immune zoominar (June 22, 2023) NEW Meet Inoviem Scientific Team (June 19 - 23, 2023) Training School on “Cell-based

and internalization of G protein-coupled receptors (GPCRs) and it participates in inflammatory and immune In vitro, we used IFNα to stimulate human salivary gland epithelial cells (HSGECs), and the results showed that IFNα activated GRP78-ATF6-CHOP apoptosis signaling, decreased cell viability, and induced apoptosis In addition, β-arrestin2 depletion downregulated GRP78-ATF6-CHOP apoptosis signaling to alleviate cell

September 2022 "Platelets are well characterized for their indispensable role in primary hemostasis to provided a substantial body of evidence demonstrating that platelets also participate in host innate immunity interactions with neutrophils enhance neutrophil activation and are often crucial to induce a sufficient immune