November 2022 Deciphering the signaling mechanisms of β-arrestin1 and β-arrestin2 in regulation of cancer metastasis "β-Arrestins are ubiquitously expressed intracellular proteins with many functions which interact directly and indirectly with a wide number of cellular partners and mediate downstream signaling. Originally, β-arrestins were identified for their contribution to GPCR desensitization to agonist-mediated Read more at the source #DrGPCR #GPCR #IndustryNews Subscribe to the Dr. GPCR Newsletter HERE

November 2022 "Recently determined structures of class C G protein-coupled receptors (GPCRs) revealed the location of allosteric binding sites and opened new opportunities for the discovery of novel modulators In this work, molecular docking screens for allosteric modulators targeting the metabotropic glutamate The mGlu5 receptor is a promising target for the treatment of psychiatric and neurodegenerative diseases Read more at the source #DrGPCR #GPCR #IndustryNews Subscribe to the Dr. GPCR Newsletter HERE

November 2022 "Dimerization of beta 2-adrenergic receptor (β2-AR) has been observed across various physiologies However, the function of dimeric β2-AR is still elusive. and the dimer was disrupted by the inverse agonists. The formation of β2-AR dimers requires cholesterol on the plasma membrane. Read more at the source #DrGPCR #GPCR #IndustryNews Subscribe to the Dr. GPCR Newsletter HERE

from dense core vesicles, and ability to activate G-protein-coupled receptors (GPCRs). These complex properties have driven the need for development of specialized tools that can sense neuropeptide Here we describe the current technological landscape in which the field is operating to decode key questions regarding these dynamic neuromodulators." Read more at the source #DrGPCR #GPCR #IndustryNews Subscribe to the Dr. GPCR Newsletter HERE

October 2022 β-arrestin1 and 2 exhibit distinct phosphorylation-dependent conformations when coupling to the same GPCR in living cells "β-arrestins mediate regulatory processes for over 800 different G However, whether β-arrestin1 and 2 respond differently for binding to the same GPCR is still unknown. Furthermore, the utilisation of advanced NanoLuc/FlAsH-based biosensors reveals distinct conformational Read more at the source #DrGPCR #GPCR #IndustryNews Subscribe to the Dr. GPCR Newsletter

October 2022 Dimerization of β2-adrenergic receptor is responsible for the constitutive activity subjected However, the function of dimeric β2-AR is still elusive. and the dimer was disrupted by the inverse agonists. The formation of β2-AR dimers requires cholesterol on the plasma membrane. Read more at the source #DrGPCR #GPCR #IndustryNews Subscribe to the Dr. GPCR Newsletter

September 2022 "Pregnant and lactating women have been discouraged from using cannabis by Health Canada cannabis use among pregnant women has presented an urgent need to investigate its physiological effects during During pregnancy, the mammary gland (MG) undergoes remodeling, which involves alveolar differentiation (THC) and cannabidiol (CBD), on MG development or MEC differentiation. Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Dual loss of regulator of G protein signaling 2 and 5 exacerbates ventricular myocyte arrhythmias and disrupts the fine-tuning of Gi/o signaling "Aims: Cardiac contractility, essential to absence of regulator of G protein signaling (RGS) 2 and 5, separately, was shown to cause G protein dysregulation Here we examined how the dual absence of RGS2 and 5 (Rgs2/5 dbKO) affects blood pressure and cardiac Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Discovery and In Vivo Evaluation of ACT-660602: A Potent and Selective Antagonist of the Chemokine Receptor CXCR3 for Autoimmune Diseases "The chemokine receptor CXCR3 is a seven-transmembrane G-protein-coupled receptor (GPCR) involved in various pathologies, in particular autoimmune diseases culminating in the discovery of the selective CXCR3 antagonist ACT-660602 (9j). Read more at the source #DrGPCR #GPCR #IndustryNews

Much focus is currently being directed towards CXCR1/2 inhibitors, as these receptors primarily induce the chemotaxis of leukocytes, especially neutrophils, during inflammation, a key process in cardiovascular disease (CVD) progression. include reducing the atherosclerotic plaque area, improving the serum lipid profile, attenuation of the damage Read more at the source #DrGPCR #GPCR #IndustryNews

chronic clinical syndrome characterized by the reduction in cardiac function and still remains the disease Despite considerable advances in pharmacological treatment, HF represents a severe clinical and social In this review, we discuss important aspects of adrenal GPCR signaling and regulation, as they pertain Particular emphasis is given to findings from the past decade and a half that highlight the emerging Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Glucagon receptor-mediated regulation of gluconeogenic gene transcription is endocytosis-dependent downstream transcription of cAMP-dependent genes. We show that epitope-tagged GCGRs undergo clathrin- and dynamin-dependent endocytosis in HEK293 and Huh We verify endocytosis-dependent induction of PCK1 expression by endogenous GCGRs in primary hepatocytes Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Design and validation of recombinant protein standards for quantitative Western blot analysis of cannabinoid CB1 receptor density in cell membranes: an alternative to radioligand binding methods to the low solubility that the hydrophobic nature imprinted by their seven transmembrane domains. Estimated values of CB1 receptor density obtained by quantitative Western blot were of the same order Read more at the source #DrGPCR #GPCR #IndustryNews

Further investigation of the signaling pathways downstream of GPR183 is needed to support the development In rodents, intrathecal injection of its ligand, 7α,25-dihydroxycholesterol (7α,25-OHC), causes time-dependent 2-dependent. Non-biased transcriptomic analyses of dorsal-horn spinal cord (DH-SC) tissues harvested at the time of Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "Recently determined structures of class C G protein-coupled receptors (GPCRs) revealed the location of allosteric binding sites and opened new opportunities for the discovery of novel modulators In this work, molecular docking screens for allosteric modulators targeting the metabotropic glutamate The mGlu5 receptor is a promising target for the treatment of psychiatric and neurodegenerative diseases Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Cholesterol-Dependent Dynamics of the Serotonin1A Receptor Utilizing Single Particle Tracking Our results show that the short-term diffusion coefficient of the receptor decreases upon cholesterol depletion, irrespective of the method of cholesterol depletion. change upon cholesterol depletion. accompanied by a reduction in diffusion coefficient for chronic cholesterol depletion.

October 2022 Bell-Evans model and steered molecular dynamics in uncovering the dissociation kinetics development have become immensely interested in predicting the drug target residence time. Here, we have implemented an optimized approach of combining the data derived from steered molecular However, our predictions were many folds shorter than those determined experimentally. Read more at the source #DrGPCR #GPCR #IndustryNews

We are postponing the Dr. GPCR Virtual Cafe with Matthew Eddy scheduled for tomorrow (Sep 29th, 2022) due to Hurricane Ian that We will provide a new rescheduling date soon. #gpcr #drgpcr

such as lysergic acid diethylamide (LSD), mescaline, and psilocybin: the desire for additional approaches With the United States Food and Drug Administration's designation of psilocybin as a "Breakthrough Therapy these drugs exert their effects at the molecular level. Here we review the current knowledge regarding the molecular details of psychedelic drug actions and Read more at the source #DrGPCR #GPCR #IndustryNews

Much focus is currently being directed towards CXCR1/2 inhibitors, as these receptors primarily induce the chemotaxis of leukocytes, especially neutrophils, during inflammation, a key process in cardiovascular disease (CVD) progression. include reducing the atherosclerotic plaque area, improving the serum lipid profile, attenuation of the damage Read more at the source #DrGPCR #GPCR #IndustryNews

However, it is becoming increasingly clear that GPCRs show great diversity in their intracellular location Here we will discuss recent studies on the diversity of location, effectors, and signaling of GPCRs, Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 Deciphering the signaling mechanisms of β-arrestin1 and β-arrestin2 in regulation of cancer metastasis "β-Arrestins are ubiquitously expressed intracellular proteins with many functions which interact directly and indirectly with a wide number of cellular partners and mediate downstream signaling. Originally, β-arrestins were identified for their contribution to GPCR desensitization to agonist-mediated Read more at the source #DrGPCR #GPCR #IndustryNews

analysis suggests that the structures of GPCRs bound to these interaction partners available today do not reveal a clear conformational basis for signaling bias, which would have enabled the rational design no generalizable GPCR conformations conducive to binding a particular type of partner; (ii) subtle differences structures determine partner preference; or (iii) the dynamics of GPCR binding to different types of Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Genetically encoded fluorescent biosensors allow intracellular signaling dynamics to be tracked in live cells and tissues using optical detection. Our approach, described in detail here, uses adeno-associated viruses infused intracerebrally in order development and screening." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Several G-protein coupled receptors (GPCR) are upregulated in Alzheimer's Disease (AD), Yet, despite this upregulation, associated physiological effects are not observed in AD patients. This paradox solicits urgent attention to find a suitable justification for disturbed neurotransmission Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Aims: The pathophysiological mechanism(s) underlying non-alcoholic fatty liver disease ( NAFLD) have yet to be fully delineated and only a single drug, peroxisome proliferator-activated receptor Here, we sought to investigate the role of Regulator of G Protein Signaling 7 (RGS7) in hyperlipidemia-dependent hepatic dysfunction. " Read more at the source #DrGPCR #GPCR #IndustryNews

, and transduce to heterotrimeric G-proteins to generate different degrees of physiological responses Previous studies revealed how ligands with different efficacies activate GPCRs. ligands, with residue-specific functional differences. Molecular dynamics simulations support the local conformational flexibilities and different stabilities Read more at the source #DrGPCR #GPCR #IndustryNews

X-linked form of Kallmann syndrome (KS), characterized by hypogonadotropic hypogonadism and anosmia, is due We also show that the N-terminal region of anosmin 1, capable of binding to the PK2-binding domain of The whey acidic protein domain (WAP) is necessary for this modulatory activity, although data from GST domain 1 (FnIII.1) suggest the cysteine-rich (CR) and the FnIII.1 domains could assist the WAP domain Read more at the source #DrGPCR #GPCR #IndustryNews