optic nerve crush in mice "Glaucoma is an optic neuropathy and is currently one of the most common diseases The axonal degeneration that occurs before retinal ganglion neuronal loss is suggested to be involved Surprisingly, RGCs in GPR3 knockout mice were vulnerable to neural death during aging without affecting Read more at the source #DrGPCR #GPCR #IndustryNews

Several integrins directly modulate VSMC contraction by regulating calcium influx through L-type voltage-gated We determined whether SVEP1 and integrin α9β1 can regulate VSMC contraction." Read more at the source #DrGPCR #GPCR #IndustryNews

GRK2/β-arrestin2 play multiple roles in the pathological mechanisms of a wide range of diseases including heart failure, cancer, and inflammatory diseases. cell function and focuses on the pathological implications of GRK2/β-arrestin2 in various inflammatory diseases Read more at the source #DrGPCR #GPCR #IndustryNews

receptors, are involved in various biologic processes and regulation of a wide range of immune responses in different receptor 4 (CXCR4), a G-protein-coupled receptor (GPCR), has one identified natural ligand termed stromal-derived Evidence demonstrated that the ligation of SDF-1 to CXCR4 initiates several intracellular signaling pathways Read more at the source #DrGPCR #GPCR #IndustryNews

The structure, function, and involvement of adhesion GPCRs in cancer development have been discussed Read more at the source #DrGPCR #GPCR #IndustryNews

THP-1 cells were activated and differentiated into either M1 or M2 macrophages. Cell migration was detected by the Boyden chamber migration assay, performed on macrophages derived from Read more at the source #DrGPCR #GPCR #IndustryNews

In this study, for the first time, we demonstrate the nuclear localization of H2R in lymphatic endothelial unresolved questions, such as the functional relevance of this localization, and whether H2R can contribute directly In this aspect, our present data shed new light on the unexplored H2R signaling mechanisms. Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Oxysterols induce the migration of B-lymphocytes and dendritic cells to interfollicular through binding the EBI2 (GPR183) to stimulate effective adaptive immunity and antibody production during Aberrant EBI2 signaling is implicated in inflammatory bowel disease, sclerosis, and infectious disease of therapeutic approaches that target EBI2-linked diseases." Read more at the source #DrGPCR #GPCR #IndustryNews

Here, we discuss recent crystal structures of inactive C5aR1 in terms of an inverted orientation of helix By comparing two C5aR receptors C5aR1 and C5aR2 we explained differences between their signaling pathways By means of molecular dynamics we explained why C5aR2 cannot transduce signal through the G protein pathway of local and global changes in the transmembrane domain induced by interactions with the Gα subunit Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Single particle cryogenic-electron microscopy (cryo-EM) is used extensively to determine Although a similar strategy has the potential to broadly facilitate cryo-EM structure determination of GPCRs alone without signaling protein, the critical determinants that make this approach successful Here, we address this shortcoming by exploring different fusion protein designs, which lead to structures Read more at the source #DrGPCR #GPCR #IndustryNews

recruiting GPR84 agonists "In order to avoid a prolonged pro-inflammatory neutrophil response, signaling downstream and analysis of subcellular fractions revealed a cytosolic localization. " Read more at the source #DrGPCR

protein-coupled receptor (GPCR) kinases (GRKs) are associated with the pathophysiology of Alzheimer's disease However, GRKs have not been directly implicated in regulation of the amyloid-β (Aβ) pathogenic cascade Here, we determine that GRKs phosphorylate a non-canonical substrate, anterior pharynx-defective 1A ( Further molecular dynamics simulation studies reveal an interaction between the βarr2 finger loop domain Read more at the source #DrGPCR #GPCR #IndustryNews

A variety of ligands for CB1 receptors have been developed as promising drug candidates for the treatment of neurological disorders. These advances have paved the way for development of novel ligands for different therapeutic applications In this review, we describe the structural determinants for modulation of CB1 receptors by different types of ligands, as well as the differences between CB1 and its homologous, the CB2 receptor.

August 2022 "Background: Activation of signaling effectors by G-protein coupled receptors (GPCRs) depends on different molecular mechanisms triggered by conserved amino acid residues. focused on the G-protein signaling state, the mechanism for β-arrestin signaling by CB1 is not yet well defined indicated that transmembrane helix 7 (TMH7) and the highly conserved NPXXY motif can be subject to different participate in a molecular mechanism to trigger β-arrestin recruitment. " Read more at the source #DrGPCR

of human A 2A AR in lipid nanodiscs for 19 F-NMR and single-molecule fluorescence spectroscopy "We describe 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

Besides their appearance on the (illicit) drug market, e.g. as new psychoactive substances, their potential This group of substances demonstrates a broad structural variety, leading to insufficiently described Additionally, several variables are discussed that one should consider when attempting to compare functional outcomes from different studies, both linked to the specific assay mechanism and linked to its specific Read more at the source #DrGPCR #GPCR #IndustryNews 5-HT2AR, GPCR, hallucinogens, in vitro assay, psychedelics

📌Our mission is to bring together all key players under one umbrella to co-exist in the @DrGPCR Ecosystem ➡️ https://bit.ly/3wQNZDg #gpcr #drgpcr

Do you hustle around looking for information about your favorite #GPCR? No need for that anymore! Dr. GPCR has it for you! 🔔 Subscribe to our monthly newsletter for FREE! ➡️ https://bit.ly/3cCI4em #gpcr #drgpcr

The program of the Dr. GPCR Summit from October 10th to the 16th is taking shape. Check it out today but first become a Dr. GPCR Ecosystem site member, which is free! Sign up now ➡️ https://bit.ly/3eaO5PH #gpcr #drgpcr

Did you know that you can enjoy a Dr. GPCR Ecosystem paid membership with extra benefits? Create your own group, watch the latest podcast video before everyone else or start a discussion in the ➡️ https://www.ecosystem.drgpcr.com/plans-pricing #gpcr #drgpcr

the existence of a functional gonadotropin-inhibitory hormone (GnIH) system in the European sea bass, Dicentrarchus Although GnIH1 and GnIH2 had no effect on basal CRE-luc activity, they significantly decreased forskolin-elicited However, GnIH peptides did not alter NFAT-RE-luc activity and ERK phosphorylation levels. These data indicate that sea bass GnIHR signals can be transduced through the PKA and PKC pathways, and Read more at the source #DrGPCR #GPCR #IndustryNews

Through (un)biased molecular dynamics simulations and mutagenesis experiments, we show that TM2 rearrangement findings fill a gap in the understanding of CB1 allosteric regulation and could guide the rational design Read more at the source #DrGPCR #GPCR #IndustryNews

For class B GPCRs, previous molecular dynamics (MD) simulation studies have shown PI(4,5)P2 interacting with the Glucagon receptor (GCGR), which constitutes an important target for diabetes and obesity therapeutics We demonstrate how tail composition plays a role in modulating the binding of PI(4,5)P2 lipids to GCGR This suggests differences in the regulatory function of PI(4,5)P2 between class A and class B GPCRs." Read more at the source #DrGPCR #GPCR #IndustryNews

Gγ1, Gγc, or Gγ11 in Gγ1-deficient mice and analyzed their properties. rod cells and restoration of Gαt1 expression, which is greatly reduced in Gγ1-deficient rods. In all dark-adapted transgenic lines, Gαt1 was targeted to the outer segments, reversing its diffuse localization found in Gγ1-deficient rods. Read more at the source #DrGPCR #GPCR #IndustryNews

macrophages and monocytes, and play a critical role in neuroinflammatory conditions such as Alzheimer's disease In this work we present the study of the CX3CR1 receptor employing extensive atomistic Molecular Dynamics We analyzed the receptor conformational changes and described interactions within its key regions and the bounded ligands to identify their notable differences. Read more at the source #DrGPCR #GPCR #IndustryNews

study, we compared GPR39 expression between colon cancers and tumor-adjacent tissues by retrieving TCGA data and detected the expression of GPR39 in colon cancers with qPCR and immunohistochemistry. of several other biomarkers including PPARG, EPCAM, and PD-L1 was investigated by re-analyzing TCGA data Read more at the source #DrGPCR #GPCR #IndustryNews

Using different optical biosensors to measure the activation of PTH1R and its downstream signaling, we describe here that RAMP2 acts as a specific allosteric modulator of PTH1R, shifting PTH1R to a unique Moreover, RAMP2 modulates PTH1R downstream signaling in an agonist-dependent manner, most notably increasing a new venue for highly specific modulation of GPCR function and advanced drug design." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "The bioactive lysophospholipid sphingosine-1-phosphate (S1P) acts via five different Several S1PR therapeutic drugs have been developed to treat these diseases; however, they lack receptor In this article, we describe a 2.2 Å resolution room temperature crystal structure of the human S1P5 the receptor subtype selectivity and provides a template for structure-based drug design. Read more at the source #DrGPCR #GPCR #IndustryNews