Search Results

August 2022 "G-protein-coupled receptors (GPCR) are present at the cell surface in different conformational and oligomeric states. However, how these states impact GPCRs biological function and therapeutic targeting remains incompletely known. Here, we investigated this issue in living cells for the CC chemokine receptor 5 (CCR5), a major receptor in inflammation and the principal entry co-receptor for Human Immunodeficiency Viruses type 1 (HIV-1). We used TIRF microscopy and a statistical method to track and classify the motion of different receptor subpopulations. We showed a diversity of ligand-free forms of CCR5 at the cell surface constituted of various oligomeric states and exhibiting transient Brownian and restricted motions. These forms were stabilized differently by distinct ligands. In particular, agonist stimulation restricted the mobility of CCR5 and led to its clustering, a feature depending on β-arrestin, while inverse agonist stimulation exhibited the opposite effect. These results suggest a link between receptor activation and immobilization. Applied to HIV-1 envelope glycoproteins gp120, our quantitative analysis revealed agonist-like properties of gp120s. " Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 Cell Surface Calcium-Sensing Receptor Heterodimers: Mutant Gene Dosage Affects Ca 2+ Sensing but Not G Protein Interaction "The calcium-sensing receptor is a homodimeric class C G protein-coupled receptor (GPCR) that senses extracellular Ca2+ (Ca2+o ) via a dimeric extracellular Venus flytrap (VFT) unit that activates G protein-dependent signaling via twin Cysteine-rich domains linked to transmembrane heptahelical (HH) bundles. It plays a key role in the regulation of human calcium and thus mineral metabolism. However, the nature of interactions between VFT units and HH bundles, and the impacts of heterozygous or homozygous inactivating mutations, which have implications for disorders of calcium metabolism are not yet clearly defined. Herein we generated CaSR-GABAB1 and CaSR-GABAB2 chimeras subject to GABAB -dependent endoplasmic reticulum sorting to traffic mutant heterodimers to the cell surface. Transfected HEK-293 cells were assessed for Ca2+o -stimulated Ca2+i mobilization using mutations in either the VFT domains and/or HH bundle intraloop-2 or intraloop-3. When the same mutation was present in both VFT domains of receptor dimers, analogous to homozygous neonatal severe hyperparathyroidism (NSHPT), receptor function was markedly impaired. Mutant heterodimers containing one wild-type (WT) and one mutant VFT domain, however, corresponding to heterozygous familial hypocalciuric hypercalcemia type-1 (FHH-1), supported maximal signaling with reduced Ca2+o potency. Thus two WT VFT domains were required for normal Ca2+o potency and there was a pronounced gene-dosage effect. In contrast, a single WT HH bundle was insufficient for maximal signaling and there was no functional difference between heterodimers in which the mutation was present in one or both intraloops; ie, no gene-dosage effect. Finally, we observed that the Ca2+o -stimulated CaSR operated exclusively via signaling in-trans and not via combined in-trans and in-cis signaling. We consider how receptor asymmetry may support the underlying mechanisms. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)." Read more at the source #DrGPCR #GPCR #IndustryNews

mesenchymal stem cells in multiple sclerosis patients Multiple sclerosis (MS) is a specific type of chronic immune-mediated disease in which the immune responses are almost run against the central nervous system (CNS). Chemokine/chemokine receptor axes play a pivotal role in the recruitment and oriented trafficking of immune

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

C3a, a product of C3 cleavage, which interacts with membrane-bound receptor C3aR to regulate innate immune has identified mechanistically distinct and cell type–specific roles for C3aR in regulating innate immune

placentation, uteroplacental malperfusion, oxidative stress, endoplasmic reticulum stress, dysregulated immune of the secretin/adhesion (Class B) G protein-coupled receptors in the regulation of cardiovascular system

proinflammatory glycoproteins liberated by the activation of the biochemical cascade of the complement system is a classical G-protein-coupled receptor (GPCR), whereas C5aR2 is a nonclassical GPCR that tailors immune

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

Through gene expression analysis in immune and gastrointestinal cells, we show that these isoforms emerge therapies against, for example, inflammatory bowel disease or bacterial infections of the gastrointestinal system

Another signaling pathway related to RGS4 involves the regulation of the immune response. RGS4 is expressed in various immune cells, including T cells and B cells, and has been shown to modulate immune cell activation and cytokine production. Wang, D., The essential role of G protein-coupled receptor (GPCR) signaling in regulating T cell immunity

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

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

with their receptors, are involved in various biologic processes and regulation of a wide range of immune

The chemokine receptor system is implicated in a wide range of inflammatory, autoimmune and infectious and in recent years attention has increasingly focused on cancer, where tumors hijack the chemokine system lot of effort has been put forward to target CKRs especially in cancer, nevertheless, targeting this system In the chemokine-receptor system, different chemokines are able to activate different pathways, which responses and a comprehensive understanding of the role of the chemokine receptor system in different

that regulate receptor phosphorylation and signaling termination, GRK2, which is highly expressed by immune

September 2022 "T cells are master regulators of the immune response tuning, among others, B cells, macrophages

are ancient large DNA viruses that have exploited gene capture as part of their strategy to escape immune

Expression of GPR84 is strongly up regulated in immune cells in a range of pro-inflammatory settings

receptor (GPCR), known as Mas-related G protein-coupled receptor-B2 (MRGPRB2), plays important roles in immune

is activated by the three chemokine ligands CXCL9, CXCL10, and CXCL11 and enables the recruitment of immune

Kevin Wright on his new position as Director of Targeted and Immuno-oncology at GPCR Therapeutics, our the signaling pathway of miR-19a/GRK6/GPCRs/PKC in a Chinese population Identification of S1PR4 as an immune Kevin Wright Joins GPCR Therapeutics as Director of Targeted and Immuno-oncology Sosei Heptares Adds

adhesion GPCR Latrophilin, an adhesion GPCR with galactose-binding lectin domain involved in the innate immune symptoms correlates with increased level of autoantibodies targeting vasoregulatory and autonomic nervous system Methods & Updates in GPCR Research Multi-tissue transcriptomic and serum metabolomic assessment reveals systemic

Congrats to: Monserrat Avila-Zozaya , our incredible contributor, for her fantastic article on Profiling Immune powerful applications of new cellular assays to determine GPCR ligand behavior in different functional systems

Bursaphelenchus xylophilus and B. mucronatus GPCRs in Oncology and Immunology GPCR signaling contributes to immune transition of glioblastoma Methods & Updates in GPCR Research Optogenetic Microwell Array Screening System small expression tag to enhance GPCR production in E. coli-based cell-free and whole cell expression systems

GPR84 is a Gi‐coupled class A GPCR mainly expressed in immune cells and microglia in the brain (Wojciechowicz Regarding the first question, GPR84 overexpression in immune cells in a range of pro‐inflammatory disorders

neurogenic properties GPCRs in Oncology and Immunology Chemoattractant receptor signaling in humoral immunity species with an engineered sensor A Multi-Angle Approach to Predict Peptide-GPCR Complexes: The N/OFQ-NOP System

experimental animals have shown that certain subsets of T cells express functional GLP-1R, indicating an immune

chemotaxis to the synovium "The rheumatoid arthritis (RA) inflammatory process occurs in the joints where immune