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October 2022 "The role of different G protein-coupled receptors (GPCRs) in the cardiovascular system effects of GPCRs in cardiac fibroblasts, focusing on key signaling events involved in the activation and differentiation We also review the hierarchy of signaling events driving the fibrotic response and the communications We discuss how such events may be distinct depending on where the GPCRs and their associated signaling Read more at the source #DrGPCR #GPCR #IndustryNews

Immunocytochemistry by light and electron microscopy demonstrated the localization of VLGR1 in MAMs. The absence of VLGR1 in tissues and cells derived from VLGR1-deficient mouse models resulted in alterations in the MAM architecture and in the dysregulation of the Ca2+ transient from ER to mitochondria. Our data demonstrate the molecular and functional interaction of VLGR1 with components in MAMs and point Read more at the source #DrGPCR #GPCR #IndustryNews

annotated as G protein-coupled receptor 155), a multidomain transmembrane protein that enables cholesterol-dependent By sequestering GATOR1, LYCHOS promotes cholesterol- and Rag-dependent recruitment of mTORC1 to lysosomes functions in a lysosomal pathway for cholesterol sensing and couples cholesterol concentrations to mTORC1-dependent 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 We explain in detail steps shared between the two sample preparation strategies, including expression 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 Read more at the source #DrGPCR #GPCR #IndustryNews

This work directly compares the performance of these novel deep learning-based protein modeling methods We collected the experimentally determined structures of 73 GPCRs from the Protein Data Bank. The official AlphaFold repository and RoseTTAFold web service were used with default settings to predict The larger RMSD values generated by the NN-based methods were primarily due to the differences in loop Read more at the source #DrGPCR #GPCR #IndustryNews

Neisseria meningitidis is a Gram-negative opportunistic pathogen that is responsible for causing human diseases During this process, we also characterized two mammalian N-acyl amides derived from the bovine medium macrophage cell types, but they also suppress the pro-inflammatory interleukin-17A+ population in TH 17-differentiated Read more at the source #DrGPCR #GPCR #IndustryNews

In this study, we generated and characterized human embryonic kidney 293A (HEK293A) cell lines devoid Direct activation of PKC and mutation of rat mGlu5a Ser901, a PKC-dependent phosphorylation site in the Nonetheless, we determined that mGlu5a internalization was not altered upon the loss of cPKCs or nPKCs and a receptor containing a mutated putative adaptor protein complex 2 (AP-2) interaction motif, we demonstrate Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "Single-molecule counting techniques enable a precise determination of the intracellular These details are often challenging to quantitatively assess yet are essential for our understanding signaling proteins that participate in many vital physiological functions making them a popular target for drug development. Read more at the source #DrGPCR #GPCR #IndustryNews

adhesion GPCR GPR116/ADGRF5 requires a tethered agonist-mediated activation mechanism "The mechanistic details the tethered agonist mode of activation for the adhesion GPCR ADGRF5/GPR116 have not been completely deciphered expressing a non-cleavable GPR116 mutant phenocopies the pulmonary phenotype of GPR116 knock-out mice, demonstrating Using site-directed mutagenesis and species-swapping approaches, we identified key conserved amino acids Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "Melanocortin 3 receptor (MC3R) is a G-protein coupled receptor (GPCR) that is defined as a regulator of appetite/hunger balance mechanisms mostly up to date. Despite the drastic effects of the MC3R deficiency in humans and other mammals, its cellular mechanisms Read more at the source #DrGPCR #GPCR #IndustryNews

Additionally, pull-down experiments demonstrated that YM promotes similar conformational changes in both αqQ209L and PM-restricted αqQ209L, resulting in increased binding to βγ and decreased binding to regulator RGS2, and effectors p63RhoGEF-DH/PH and phospholipase C-β. GPCR-dependent signaling by PM-restricted wild type αq is strongly inhibited by YM, demonstrating that Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "Herpesviruses are ancient large DNA viruses that have exploited gene capture as part of We discuss ligand binding, signaling, and structures of the vGPCRs in light of robust differences from Finally, we briefly discuss the therapeutic targeting of vGPCRs as future treatment of acute and chronic Read more at the source #DrGPCR #GPCR #IndustryNews

Obesity, immunological diseases and endocrine metabolic diseases are high-risk factors for the development immune tolerance, vascular inflammation and endothelial cell dysfunction. target family to date, exhibit diversity in structure and function. human diseases, such as endocrine diseases and cardiometabolic diseases. Read more at the source #DrGPCR #GPCR #IndustryNews

Using classical and enhanced molecular dynamics simulations, we show that membrane lipids are critical The observed differences in the binding affinity and cooperativity arise from the functional groups that Our results demonstrate the significance of incorporating membrane lipids as an integral component of discovery." Read more at the source #DrGPCR #GPCR #IndustryNews

fungi by macrophages "The fungal pathogen Histoplasma capsulatum (Hc) invades, replicates within, and destroys To interrogate the molecular mechanisms underlying this interaction, we conducted a host-directed CRISPR-Cas9 We demonstrated that whereas C3aR is dispensable for macrophage phagocytosis of bacteria and latex beads We showed that C3aR localizes to the early phagosome during Hc infection where it coordinates the formation Read more at the source #DrGPCR #GPCR #IndustryNews

occurs in the joints where immune cells are attracted into the synovium to promote remodeling and tissue damage Statistical analysis included Kruskal-Wallis test, T-test, or Mann-Whitney U test, according to data distribution. Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "G protein-coupled receptors (GPCRs) are of considerable interest due to their importance in a wide range of physiological functions and in a large number of Food and Drug Administration (FDA )-approved drugs as therapeutic entities. As new technologies are developed and applied to studying GPCR structure and their downstream effectors Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "The cAMP-dependent protein kinase (PKA) system represents a primary cell-signaling pathway regulates cellular metabolism and emotional and stress responses making it integral in the maintenance and dysregulation While limited, human studies infer differential regulation of the PKA system in obese compared to lean Variants identified in PKA subunit genes cause Cushing syndrome that is characterized by metabolic dysregulation Read more at the source #DrGPCR #GPCR #IndustryNews

Thus, we systematically investigated the relationship between the concentration of two distinct pro-inflammatory Furthermore, we demonstrate that the efficacy of different synthetic cannabinoid treatments with respect This indicates that different pro-inflammatory stimuli influence the capacity of microglia to synthesize , degrade, and respond to cannabinoids which has implications for the development of cannabinoid-based Read more at the source #DrGPCR #GPCR #IndustryNews

Here we developed and validated a label-free, liquid chromatography-mass spectrometry (LC-MS) based cell various target classes, with particular emphasis on those for which protein-based binding assay can be difficult In another example, this assay was applied to an ion channel target with its agonists, of which the determined Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "Pepducins are small-lipidated peptides designed from the intracellular loops of G protein-coupled Over the past 2 decades, pepducins have progressed initially from pharmacologic tools used to manipulate To date, pepducins designed from numerous GPCRs have been studied for their impact on pathologic conditions We will discuss the historic context of pepducin development for each receptor, as well as the structural Read more at the source #DrGPCR #GPCR #IndustryNews

modulate a plethora of physiological processes and mediate the effects of one-third of FDA-approved drugs Depending on which ligand activates a receptor, it can engage different intracellular transducers. However, ligand bias is very complex, making reproducibility and description challenging. The guidelines will aid consistency and clarity, as the basic receptor research and drug discovery communities Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Psychedelic research across different disciplines and biological levels is growing at a In the prospect of a psychedelic drug becoming again an approved treatment, much of these efforts have Considering the central role of the serotonin 5-HT2A receptor in the distinct effects of psychedelics in human psyche, neuropharmacology sits at the center of this debate and exploratory continuum. Read more at the source #DrGPCR #GPCR #IndustryNews

pyrazole-based agonist 1 ((S)-N-(1-(cyclobutylamino)-1-oxo-5-(piperidin-1-yl)pentan-3-yl)-1-cyclopentyl-5-(2,6-dimethoxyphenyl This compound has vastly reduced brain penetration and is devoid of significant off-target liability. Read more at the source #DrGPCR #GPCR #IndustryNews

versatile molecular tools to study G protein-coupled receptors (GPCRs) and can be used for a range of different Here, we report the structure-based development of fluorescent ligands targeting the intracellular allosteric binding site (IABS) of the CC chemokine receptor 2 (CCR2), a class A GPCR that has been pursued as a drug By means of these studies, we developed 14 as a fluorescent CCR2 ligand, enabling cell-free as well Read more at the source #DrGPCR #GPCR #IndustryNews

One potential solution is to develop analgesics that act at targets other than opioid receptors. These can be used either as stand-alone therapeutics or to improve the safety profile of opioid drugs then used electrophysiological recordings to evaluate the effects of YM-254890 on the excitability of dorsal root ganglion (DRG) nociceptor neurons." Read more at the source #DrGPCR #GPCR #IndustryNews

pharmacology assay toolbox to characterize ligand efficacy at the level of receptor proteins instead of downstream characterization of a NanoBRET-based conformational histamine H3 receptor (H3R) biosensor that allowed the detection ready-to-use, high-throughput alternative for radioligand binding assays that in addition can also detect Read more at the source #DrGPCR #GPCR #IndustryNews