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 It plays a key role in the regulation of human calcium and thus mineral metabolism. 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.

are attracted into the synovium to promote remodeling and tissue damage. A higher expression in the mRNA for GPR15 was identified in early RA subjects. GPR15 and GPR15L are present in the synovial tissue of RA patients and GPR15L promotes migration of PBMCs from RA patients and healthy subjects. therapeutic approach in RA."

September 2022 PLC-IP3-ORAI pathway participates in the activation of the MRGPRB2 receptor in mouse peritoneal However, the opening of ion channels mediated by MRGPRB2 activation remains unclear. were correlated with extracellular calcium concentration. The increases in [Ca2+]i and voltage-dependent current caused by MRGPRB2 activation were blocked by U73122 The voltage-dependent current induced by MRGPRB2 was inhibited by calcium-activated chlorine channel

Nocturnal asthma is characterized by heightened bronchial reactivity at night, and plasma melatonin concentrations receptors are expressed on airway smooth muscle; whether they regulate intracellular cyclic AMP (cAMP) and calcium concentrations ([Ca2+]i), which modulate airway smooth muscle tone; and whether they promote airway We detected the mRNA and protein expression of the melatonin MT2 but not the MT1 receptor in native human Activation of melatonin MT2 receptors with either pharmacological concentrations of melatonin (10-100

and inactivation of downstream signaling. G-protein signaling activates the MAPK Fus3, which phosphorylates the RGS; however, the role of this Surprisingly, phosphorylation of the RGS promotes completion of cytokinesis before pheromone-induced Completion of cytokinesis in the presence of pheromone is promoted by the kelch-repeat protein, Kel1 These data lead us to a model where Kel1 promotes completion of cytokinesis before pheromone-induced

September 2022 GPR84 signaling promotes intestinal mucosal inflammation via enhancing NLRP3 inflammasome activation in macrophages "The putative medium-chain free fatty acid receptor GPR84 is a G protein-coupled Here we demonstrate that GPR84 is highly upregulated in inflamed colon tissues of active ulcerative colitis GPR84 activation imposes pro-inflammatory properties in colonic macrophages through enhancing NLRP3 inflammasome activation, while the loss of GPR84 prevents the M1 polarization and properties of proinflammatory macrophages

Intracellular calcium ([Ca2+]i) signaling is a critical regulator of chondrogenesis, chondrocyte differentiation Calcium (Ca2+) signaling is known to direct processes that govern chondrocyte gene expression, protein signaling transducers; however, such approaches can lack specificity and/or precision regarding Ca2+ activation One such platform is the chemogenetic DREADD (designer receptor exclusively activated by designer drugs ) hM3Dq, which activates [Ca2+]i signaling via the Gαq-PLCβ-IP3-ER pathway upon clozapine N-oxide (CNO

hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor 1 (PTH1R) and activate Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged Gs activation , whereas PTHrP evokes transient Gs activation with reduced bone-resorption effects.

hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor 1 (PTH1R) and activate Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged Gs activation , whereas PTHrP evokes transient Gs activation with reduced bone-resorption effects.

Instead, fast calcium signals in PFC astrocytes are time locked to dopamine release and are mediated Thus, we identify astrocytes as active players in dopaminergic signaling in the PFC, contributing to

September 2022 CCL25/CCR9 interaction promotes the malignant behavior of salivary adenoid cystic carcinoma receptor 9 (CCR9), an organ-specific chemokine receptor, interacts with its exclusive ligand CCL25 to promote Western blot and RT–qPCR assays were carried out to measure the downstream factors of the interaction

signaling via the GPCRs, β2-adrenergic receptor (β2AR), and metabotropic glutamate receptor 2 (mGluR2) promotes hyperphosphorylation of tau, we hypothesized that β-arrestin1 represents a point of convergence for such pathogenic activities destabilizing microtubules and impeding p62/SQSTM1 autophagy flux by interfering with p62 body formation, which promotes

liver disease (NAFLD) have yet to be fully delineated and only a single drug, peroxisome proliferator-activated

That precursor is inactive, but proteases from the coagulation and fibrinolytic cascades, as well as from inflammatory reactions, process the C-terminus of chemerin to first activate it and then subsequently inactivate it. and inactivation of chemerin. Methods of identifying and determining the levels of different chemerin forms in both mass and activity

of the Stalk sequence with the transmembrane regions promote their coupling with G-proteins. Comparison between a predicted model of inactive receptor structure and self-activated Cryo-EM highlighted TM7 and TM1 are characteristic of ADGRL3 self-activation. -Q., et al., Structural basis for the tethered peptide activation of adhesion GPCRs. Boucard, A.A., Self-activated adhesion receptor proteins visualized.

GPCR Symposium on GPCR activation and signaling sessions. Let’s dive into the Classified GPCR News from March 18th to 24th, 2024 GPCR Activation and Signaling Calcium-Driven In Silico Inactivation of a Human Olfactory Receptor Deciphering the role of glycosaminoglycans protein-coupled receptor-mediated autophagy in health and disease GPCR Binders, Drugs, and more Elucidation of active in cancer Methods & Updates in GPCR Research A multicolor suite for deciphering population coding of calcium

Capturing the dynamics of GPCR activation has always been a challenge because G protein activation in cells occurs in less than a second, reflecting the transient nature of these active states. The AHD transitioning to a closed conformation prompts the β2–β3 loop to move away from the α5 helix, targeting specific steps within the G-protein activation cycle. Time-resolved cryo-EM of G-protein activation by a GPCR. Nature (2024).

September 2022 "Receptor-activity-modifying proteins (RAMPs) are ubiquitously expressed membrane proteins Using different optical biosensors to measure the activation of PTH1R and its downstream signaling, we specific allosteric modulator of PTH1R, shifting PTH1R to a unique preactivated state that permits faster activation These data uncover a critical role of RAMPs in the activation and signaling of a GPCR that may provide

September 2022 Biased GPCR signaling by the native parathyroid hormone-related protein 1 to 141 relative hormone (PTH)-related protein (PTHrP) is indispensable for the development of mammary glands, placental calcium , (ii) receptor signaling via Gs and Gq, and (iii) receptor internalization and recycling that the native show that the molecular basis for biased signaling differences between PTHrP1-36 and properties of native Taken together, our results contribute to a better understanding of the biased signaling process of a native

A much smaller conformational change of helix VI upon activation than previously solved class A GPCR-Gi

October 2022 "The activity of dopamine neurons is dependent on both intrinsic properties and afferent One potent form of inhibition is mediated by the activation of two inhibitory G protein-coupled receptors Each of these receptors activates G protein-coupled inwardly rectifying potassium (GIRK) channels. Recordings in brain slices have shown that co-activation using saturating concentrations of agonists The kinetics of the current induced by transient receptor activation is prolonged in each case.

September 2022 Interacting binding insights and conformational consequences of the differential activity of cannabidiol with two endocannabinoid-activated G-protein-coupled receptors "Cannabidiol (CBD), the Notably, while CBD is able to antagonize some GPCRs in the endocannabinoid system, it also seems to activate Namely, CBD has been suggested to directly trigger receptor’s activation, stabilize CB1 inactive conformations Prompted by these results, we investigated the role of the CBD compound on the CB1 receptor using similar

Cryo-electron microscopy studies revealed a drastic conformational change upon activation and a unique However, little is known about the mechanism for GP coupling and activation for class C GPCRs. Here, we use molecular metadynamics computations to predict the mechanism by which the inactive GP induces conformational changes in the GABABR transmembrane domain (TMD) to form an intermediate pre-activated We find that the inactive GP first interacts with TM3, which further leads to the TMD rearrangement and

October 2022 Keratinocyte-derived defensins activate neutrophil-specific receptors Mrgpra2a/b to prevent Here, we discovered that the epithelial-cell-derived antimicrobial peptides defensins activated orphan Activation of Mrgpra2 by defensin triggered neutrophil release of IL-1β and CXCL2 which are vital for epithelial-neutrophil signaling via the defensin-Mrgpra2 axis in maintaining healthy skin ecology and promoting

October 2022 Dimerization of β2-adrenergic receptor is responsible for the constitutive activity subjected Here, we revealed that dimerization of β2-AR is responsible for the constitutive activity of β2-AR generating The cholesterol did not interfere with the agonist-induced activation of monomeric β2-AR, unlike the

of GPCRs2. β-arrestins are cytosolic proteins that translocate to the plasma membrane upon GPCR activation Lipid molecules, such as phosphoinositides, can bind to specific domains of β-arrestins, promoting their The increase in active β-arrestin molecules and the time they spend diffusing on the plasma membrane Plasma membrane preassociation drives β-arrestin coupling to receptors and activation. Molecular mechanism of GPCR-mediated arrestin activation.

October 2022 Structural perspectives on the mechanism of signal activation, ligand selectivity and allosteric

protein-coupled receptor 155), a multidomain transmembrane protein that enables cholesterol-dependent activation bound to the amino-terminal permease-like region of LYCHOS, and mutating this site impaired mTORC1 activation cholesterol concentrations, LYCHOS bound to the GATOR1 complex, a guanosine triphosphatase (GTPase)-activating By sequestering GATOR1, LYCHOS promotes cholesterol- and Rag-dependent recruitment of mTORC1 to lysosomes