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

GPR125 (ADGRA3), an orphan adhesion GPCR, has been shown to modulate planar cell polarity in gastrulating zebrafish, but its biochemical properties and role in mammalian cells have remained largely unknown. and human embryonic kidney HEK293 cells. Furthermore, in polarized MDCK cells, GPR125 is exclusively recruited to the basolateral domain of the in Matrigel 3D culture of MDCK cells.

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

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 "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 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

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

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

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

The immune system depends on chemokines to direct cell migration during immune surveillance and inflammation CCR2 is an example of a dual-function receptor that directly regulates both cell migration and scavenging Scavenging allows cells to continuously migrate by remaining responsive to chemokines, it dampens the , and CCR5 switch purely to scavenging (D'Amico G. et al. 2000), becoming incapable of promoting cell migration, a phenomenon which is likely to be mediated by changes in the cell motility machinery with

positioning of the cannabinoid CB1 receptor on the outer mitochondrial membrane of skeletal and myocardial cells T., Gardella, T. J., & Vilardaga, J. P. (2009). C., Götz, K., Sungkaworn, T., Lohse, M. J., & Calebiro, D. (2016). Z., Wilderman, A., Katakia, T., McCann, T., Yokouchi, H., Zhang, L., Corriden, R., Liu, D., Feigin, M GPCRomics: GPCR Expression in Cancer Cells and Tumors Identifies New, Potential Biomarkers and Therapeutic

complex, including vesicle-associated membrane protein 2 (VAMP2), regulate this last step toward the cell characterized, the mechanisms that modulate the delivery of GPCRs to the membrane cell still need to be well known [3-5]. in regulating dopamine D2 receptor signaling by controlling the trafficking of the receptor to the cell presence of VAMP2, specifically in recycling vesicles containing MOR but not B2AR or TFR in HEK293 cells

ERK signaling, tightly regulated through feedback mechanisms and spatial localisation within the cell Extracellular Signal-Regulated Kinase: A Regulator of Cell Growth, Inflammation, Chondrocyte and Bone Cell Receptor-Mediated Gene Expression. Cells, 10(10), 2509. Volmat, V., & Pouysségur, J. (2001). Biology of the Cell, 93(1‐2), 71-79. Wei, H., Ahn, S., Shenoy, S. K., Karnik, S.

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. 

Using CRISPR-Cas9 knockout HEK cells lacking Gs proteins, a study by Stallaert et al. in 2017 showed GPCR priming represents a compelling area of research that promises to deepen our understanding of cellular Receptor Transactivation by the β(2)-Adrenergic Receptor Increases Intracellular Ca(2+) in Nonexcitable Cells

Indicators Design of an effective small expression tag to enhance GPCR production in E. coli-based cell-free and whole cell expression systems A high-throughput structural dynamics approach for identification Oliver Hartley, was at the PEGS Europe Novartis pays Legend $100M upfront to give solid tumor CAR-T the T-Charge treatment Innovation And Healthcare Meet At Novartis Neurocrine Biosciences Announces Settlement 2 Study Completes Recruitment of Patients Sanyou Bio's Evolution of Bioprocess Enhancement for CHO Cell

determine the functional consequences of every possible amino acid change at each position in a protein, as well T., Baltos, J.-A., Thomas, T., Nguyen, T. D., Muñoz, L. L., Gregory, K. J., White, P. T. (2016).

They have also been used as biosensors to monitor conformational changes of GPCRs in living cells. Most Nbs can be functionally expressed as genetically encoded intrabodies within a eukaryotic cell. correlating structural or dynamic features observed in vitro with functional observations from living cells T., Rosenbaum, D. M., Thian, F. S., Kobilka, T. S., Schnapp, A., Konetzki, I., Sunahara, R.

Human cells express over 800 G-protein-coupled receptors (GPCRs) to facilitate communication with the Capturing the dynamics of GPCR activation has always been a challenge because G protein activation in cells like cryo-EM in solving complex biological puzzles and underscores the importance of understanding cellular of other complex signaling pathways and molecular interactions, offering a deeper understanding of cellular T. & Gainetdinov, R. R. Physiological roles of G protein-coupled receptor kinases and arrestins.

integral to metabolic regulation, particularly in glucose homeostasis and insulin secretion, making it a well-established Kenakin, T. and A. Cell Metab, 2018. 27 (4): p. 740-756. 3.          Cell, 2016. 165 (7): p. 1632-1643. 6.         

their AlphaFold2 predicted water-soluble QTY variants and uncovering the natural mutations of L->Q, I->T, F->Y and Q->L, T->I and Y->F Industry News Sosei Heptares Doses First Subject in Phase 1 Trial with