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follicle-stimulating hormone receptor (FSHR) belongs to the glycoprotein hormone receptors, a subfamily of G-protein-coupled

October 2022 "Psychedelics, also known as classical hallucinogens, affect processes related to perception, cognition and sensory processing mostly via the serotonin 5-HT2A receptor (5-HT2AR). This class of psychoactive substances, which includes lysergic acid diethylamide (LSD), psilocybin, mescaline and the substituted amphetamine 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), is receiving renewed attention for their potential therapeutic properties as it relates to psychiatric conditions such as depression and substance use disorders. Current studies focused on the potentially clinical effects of psychedelics on human subjects tend to exclude sex as a biological variable. Much of the understanding of psychedelic pharmacology is derived from rodent models, but most of this preclinical research has only focused on male mice. Here we tested the effects of DOI on head-twitch behavior (HTR) - a mouse behavioral proxy of human psychedelic potential - in male and female mice. DOI elicited more HTR in female as compared to male C57BL/6J mice, a sex-specific exacerbated behavior that was not observed in 129S6/SvEv animals. Volinanserin (or M100907) - a 5-HT2AR antagonist - fully prevented DOI-induced HTR in male and female C57BL/6J mice. Accumulation of inositol monophosphate (IP1) in the frontal cortex upon DOI administration showed no sex-related effect in C57BL/6J mice. However, the pharmacokinetic properties of DOI differed among sexes - brain and plasma concentrations of DOI were lower 30 and 60 min after drug administration in female as compared to male C57BL/6J mice. Together, these results suggest strain-dependent and sex-related differences in the behavioral and pharmacokinetic profiles of the 5-HT2AR agonist DOI in C57BL/6J mice, and support the importance of studying sex as a biological variable in preclinical psychedelic research." Read more at the source #DrGPCR #GPCR #IndustryNews

GPCRs Are Optimal Regulators of Complex Biological Systems and Orchestrate the Interface between Health and Disease GPCRs arguably represent the most effective current therapeutic targets for a plethora of diseases. GPCRs also possess a pivotal role in the regulation of the physiological balance between healthy and pathological conditions; thus, their importance in systems biology cannot be underestimated. The molecular diversity of GPCR signaling systems is likely to be closely associated with disease-associated changes in organismal tissue complexity and compartmentalization, thus enabling a nuanced GPCR-based capacity to interdict multiple disease pathomechanisms at a systemic level. GPCRs have been long considered as controllers of communication between tissues and cells. This communication involves the ligand-mediated control of cell surface receptors that then direct their stimuli to impact cell physiology. Given the tremendous success of GPCRs as therapeutic targets, considerable focus has been placed on the ability of these therapeutics to modulate diseases by acting at cell surface receptors. In the past decade, however, attention has focused upon how stable multiprotein GPCR superstructures, termed receptorsomes, both at the cell surface membrane and in the intracellular domain dictate and condition long-term GPCR activities associated with the regulation of protein expression patterns, cellular stress responses and DNA integrity management. The ability of these receptorsomes (often in the absence of typical cell surface ligands) to control complex cellular activities implicates them as key controllers of the functional balance between health and disease. A greater understanding of this function of GPCRs is likely to significantly augment our ability to further employ these proteins in a multitude of diseases. Read full article

October 2022 "Background: Uncoupling proteins (UCPs) are unpaired electron carriers that uncouple oxygen intake by the electron transport chain from ATP production in the inner membrane of the mitochondria. The physiological activities of UCPs have been hotly contested, and the involvement of UCPs in the pathogenesis and progression of diabetes mellitus is among the greatest concerns. UCPs are hypothesised to be triggered by superoxide and then reduce mitochondrial free radical production, potentially protecting diabetes mellitus patients who are experiencing oxidative stress. Objectives: The objectives of the study are to find out the newest ways to treat diabetes mellitus through protein uncoupling." Read more at the source #DrGPCR #GPCR #IndustryNews

Characterization of a new WHIM syndrome mutant reveals mechanistic differences in regulation of the chemokine receptor CXCR4 WHIM syndrome is a rare immunodeficiency disorder that is characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. While several gain-of-function mutations that lead to C-terminal truncations, frame shifts and point mutations in the chemokine receptor CXCR4 have been identified in WHIM syndrome patients, the functional effect of these mutations are not fully understood. Here, we report on a new WHIM syndrome mutation that results in a frame shift within the codon for Ser339 (S339fs5) and compare the properties of S339fs5 with wild type CXCR4 and a previously identified WHIM syndrome mutant, R334X. The S339fs5 and R334X mutants exhibited significantly increased signaling compared to wild type CXCR4 including agonist-promoted calcium flux and extracellular signal-regulated kinase activation. This increase is at least partially due to a significant decrease in agonist-promoted phosphorylation, β-arrestin binding, and endocytosis of S339fs5 and R334X compared to wild type CXCR4. Interestingly, there were also significant differences in receptor degradation, with S339fs5 having a very high basal level of degradation compared to that of R334X and wild type CXCR4. In contrast to wild type CXCR4, both R334X and S339fs5 were largely insensitive to CXCL12-promoted degradation. Moreover, while basal and agonist-promoted degradation of wild type CXCR4 was effectively inhibited by the CXCR4 antagonist TE-14016, this had no effect on the degradation of the WHIM mutants. Taken together, these studies identify a new WHIM syndrome mutant, CXCR4-S339fs5, that promotes enhanced signaling, reduced phosphorylation, β-arrestin binding and endocytosis, and a very high basal rate of degradation that is not protected by antagonist treatment. Read full article

G.; Ishiguro, H.; Horiuchi, Y.; Onaivi, E. S. J.; Wang, J.; Wu, M.; Katritch, V.; Zhao, S.; Kunos, G.; Bohn, L. M.; Makriyannis, A.; Stevens, R. G.; Manera, C. .; Moes, S.; Beck, J.; Nettekoven, M.; Benito-Cuesta, I.; Grande, T.; Drawnel, F.; Widmer, G.; Holzer S.; Leonetti, F.; Colabufo, N. A.; Mangiatordi, G. F.; Nicolotti, O.; Perrone, M.

One fascinating aspect of the cellular signaling network is the crosstalk between G protein-coupled receptors involvement in a myriad of physiological processes, mediate mostly signaling through heterotrimeric G this study was: How do growth factors, specifically through RTKs, modulate canonical heterotrimeric G Notably, the Y320F mutation restored some signaling capabilities, emphasizing Tyr320's role in membrane Reference Roy, S., Sinha, S., Silas, A. J., Ghassemian, M., Kufareva, I., & Ghosh, P. (2024).

GPCRs, G proteins, and arrestins on endosomal membranes3,4. , S. K., Karnik, S. S., Hunyady, L., Luttrell, L. M., & Lefkowitz, R. J. (2003). , Bénard, G., Ramos, A., Reguero, L., Arrabal, S., Elezgarai, I., Gerrikagoitia, I., Suarez, J., Rodríguez A., Sriram, K., Wiley, S.

; Rinken, A.; Kopanchuk, S. ; Kopanchuk, S.; Rinken, A. D2 Dopamine Receptor-G Protein Coupling. ; Pockes, S. -J.; Veiksina, S.; Kõlvart, K. R.; Min, M.; Kopanchuk, S.; Rinken, A.

S. (2002) National Human Genome Research Institute. S., Caron, M. G., Lefkowitz, R. J., & Strader, C. D. (1986). G., & Schiöth, H. B. (2003). M., Pérez-Hernández, G., Batebi, H., Gao, Y., Eskici, G., Seven, A. W., & Skiniotis, G. (2023).

Notably, G-protein-coupled receptors (GPCRs), representing the biggest drug target, have been revealed Historically, drug discovery efforts targeting GPCRs focused on G-protein-dependent signaling pathways Recent research has unveiled the emergence of G-protein-independent pathways, particularly those involving References Eishingdrelo, H., & Kongsamut, S. (2013). Wei, H., Ahn, S., Shenoy, S. K., Karnik, S. S., Hunyady, L., Luttrell, L. M., & Lefkowitz, R.

Its biggest advantage is the presence of Cys residues in proteins, although sometimes S-S bridge reduction G.; Boström, J.   (2) Sam, S.; Touahir, L.; Salvador Andresa, J.; Allongue, P.; Chazalviel, J. In Comprehensive Analytical Chemistry ; Verma, S. K., Das, A.   (4) Fontaine, S. D.; Reid, R.; Robinson, L.; Ashley, G. W.; Santi, D. V.

In all these situations, chemokines interact with seven-transmembrane chemokine-type G protein-coupled In humans there are approximately 45 chemokines, 19 chemotactic or G-protein coupled chemokine receptors protein-coupled CKRs that bind to the same ligand(s) (Nibbs, R. J.; Graham, G. J., 2013). example of a dual-function receptor that directly regulates both cell migration and scavenging (Volpe S.

Khaled Abd-Elrahman, Stephen Ferguson et al. /o protein responses of some native GPCRs in neurons Beyond the Nucleus: Plastic Chemicals Activate G and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein

G protein-coupled receptors (GPCRs) are a vast family of membrane-bound proteins crucial for transmitting avoiding interactions with non-cognate G proteins [1]. prepare the GPCR in a manner that optimizes subsequent cognate G protein activation. landscape where non-cognate G proteins play a critical preparatory role. Proc Natl Acad Sci U S A, 2020. 117(35): p. 21723-21730. 2.     

includes congrats to: Clementine E Philibert and Mikel Garcia-Marcos for their work on Smooth operator(s) : dialing up and down neurotransmitter responses by G-protein regulators András D Tóth, Gábor Turu, and László Hunyady for their research on Functional consequences of spatial, temporal and ligand bias of G challenges Modulating Vertebrate Physiology by Genomic Fine-Tuning of GPCR Functions Smooth operator(s) , temporal and ligand bias of G protein-coupled receptors Inverse Regulation of C-C Chemokine Receptor

April 2022 Read more at the source #DrGPCR #GPCR #IndustryNews

G protein-coupled receptors (GPCRs) are membrane-bound proteins that sense external stimuli and relay Bouvier, M., Oligomerization of G-protein-coupled transmitter receptors.   Graaf, C., et al., Glucagon-Like Peptide-1 and Its Class B G Protein-Coupled Receptors: A Long March Proc Natl Acad Sci U S A, 2012. 109 (45): p. 18607-12. 8.          Wootten, D., et al., Allostery and Biased Agonism at Class B G Protein-Coupled Receptors.  

A., Trumpp-Kallmeyer, S., & Humblet, C. (1998). G-protein coupled receptors: models, mutagenesis, and drug design. G., Irwin, J. J., Shoichet, B. K., & Jacobson, K. A. (2010). B., Chang, B., & Peisajovich, S. G. (2017). M., & Fields, S. (2014). Deep mutational scanning: a new style of protein science.

They manage this by interacting with G-proteins. What happens when a GPCR is activated? undergoes a conformational change to its active state (PDB ID: 3SN6); and (C) an active GPCR binds a G protein (PDB ID: 3SN6), which subsequently promotes nucleotide release from, and activation of, the G Orphan G protein-coupled receptors: The role in CNS disorders . Biomed Pharmacother. 2018 Feb;98:222-232. doi: 10.1016/j.biopha.2017.12.056 Azam S, Haque ME, Jakaria

s Director Stephen A. Deadline February 12, 2023 Current Technologies To Understand G-Protein-Coupled Receptor Molecular Pharmacology

Upon activation, chemokine receptors coupe to the Gαi class of heterotrimeric G proteins, which, in turn protein–coupled chemokine receptors that bind to the same ligand(s) (R. an example of a dual-function receptor that directly regulates both cell migration and scavenging (S. Grundmann et al. 2018), did not affect chemokine scavenging, consistent with prior work (S. Scavenging may allow cells to continuously migrate by remaining responsive to chemokines (S.

K., Odongo, S., Radwanska, M., & Magez, S. (2023). Nanobodies to Study G Protein-Coupled Receptor Structure and Function. G., Choi, H. J., Fung, J. J., Pardon, E., Casarosa, P., Chae, P. S., Devree, B. T., Rosenbaum, D. S., Kobilka, T. S., Schnapp, A., Konetzki, I., Sunahara, R. K., Gellman, S. Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor.

This Week’s Highlights: G protein-coupled receptor (GPCR) pharmacogenomics Miles D Thompson , David Reiner-Link , Alessandro Berghella , Brinda K Rana , G Enrico Rovati , Valerie Capra , Caroline M Gorvin , Alexander S Hauser Calcineurin-fusion facilitates cryo-EM structure determination of a Family A GPCR Joshua Levitz , Ben Jones , Johannes Broichhagen Design of allosteric modulators that change GPCR G Protease-Activated Receptor-1 IgG Autoantibodies in Patients with COVID-19 Signaling by neutrophil G

diverse responses based on cell-specific G protein expression. S. F et al. 2021, Chen, H. et al. 2022). G. 2021). S. et al. 2022). S. F. et al. 2021).

Research Needs Built on more than two decade A GPCR Internalization Tool Designed for Real Research Needs s supports every stage of the signaling cascade: GPCR ligand binding  – TR-FRET, radioligand, Tag-lite® G-protein programs, and partner content, we help scientists connect, collaborate, and innovate in the world of G

G protein-coupled receptor signaling analysis using homogenous time-resolved Förster resonance energy Source: Navarro G, Sotelo E, Raïch I, Loza MI, Brea J, Majellaro M. References Navarro G, Sotelo E, Raïch I, Loza MI, Brea J, Majellaro M. G protein-coupled receptor signaling analysis using homogenous time-resolved Förster resonance energy Degorce F, Card A, Soh S, Trinquet E, Knapik GP, Xie B.

GPCR Activation and Signaling Rules and mechanisms governing G protein coupling selectivity of GPCRs receptor trafficking GPCR Binders, Drugs, and more An inverse agonist of orphan receptor GPR61 acts by a G Serotonin Receptor 2C Signaling GPCRs in Oncology and Immunology CaaX-motif-adjacent residues influence G solid tumors for first-in-child use of PRL3-zumab humanized antibody Activation of PI3K/Akt pathway by G acute migraines Addex mGlu2 NAM Cognition Program Receives €4 Million Grant Confo Therapeutics Appoints Stephen

Jang W, Senarath K, Feinberg G, Lu S, Lambert NA. Visualization of endogenous G proteins on endosomes and other organelles. eLife. 2024 Nov 8; 13:RP97033 Navarro G, Sotelo E, Raïch I, Loza MI, Brea J, Majellaro M.

composition, organization, and physical properties might impact ligand binding, receptor activation, G internalization via interaction with the adaptor protein 2 (AP2) and clathrin heavy chain mediating G K., Selent, J., Hill, S. J., & Calebiro, D. (2023). Classical and new roles of b-arrestins in the regulation of G-protein-coupled receptors. Nat. Rev. Reiter, E., Ahn, S., Shukla, A.K., and Lefkowitz, R.J. (2012).