August 2022 "Abstract Chemokines such as stromal derived factor 1 and their G protein coupled receptors are well-known regulators of the development and functions of numerous tissues. C-X-C motif chemokine ligand 12 (CXCL12) has two receptors: C-X-C chemokine motif receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3). ACKR3 has been described as an atypical "biased" receptor because it does not appear to signal through G proteins and, instead, signals solely through the β-arrestin pathway. In support of this conclusion, we have shown that ACKR3 is unable to signal through any of the known mammalian G α isoforms and have generated a comprehensive map of the G α activation by CXCL12/CXCR4. We also synthesized a series of small molecule ligands which acted as selective agonists for ACKR3 as assessed by their ability to recruit β-arrestin to the receptor. Using select point mutations, we studied the molecular characteristics that determine the ability of small molecules to activate ACKR3 receptors, revealing a key role for the deeper binding pocket composed of residues in the transmembrane domains of ACKR3. The development of more selective ACKR3 ligands should allow us to better appreciate the unique roles of ACKR3 in the CXCL12/CXCR4/ACKR3-signaling axis and better understand the structural determinants for ACKR3 activation. SIGNIFICANCE STATEMENT: We are interested in the signaling produced by the G protein coupled receptor atypical chemokine receptor 3 (ACKR3), which signals atypically. In this study, novel selective ligands for ACKR3 were discovered and the site of interactions between these small molecules and ACKR3 was defined. This work will help to better understand the unique signaling roles of ACKR3." Read more at the source #DrGPCR #GPCR #IndustryNews

GPCRs in Neuroscience DRD1 signaling modulates TrkB turnover and BDNF sensitivity in direct pathway striatal Transcriptomic analysis of human cytomegalovirus to survey the indirect effects on renal transplant recipients

We have previously reported that the MC4R forms homodimers, affecting receptor Gs signaling properties In this study, we analyzed effects of inhibiting homodimerization on Gq/11 signaling using previously In summary, our study shows that inhibiting homodimerization has a setmelanotide-like effect on Gq/11

(HCMV) viremia has been linked to adverse "indirect effects" among transplant patients. HCMV-created immunomodulatory mechanisms could be associated with the indirect effects. effects of HCMV. effects caused by HCMV infection in transplant patients." Tags Human cytomegalovirus , Indirect effects , RNA-Seq , Renal transplantation , Transcriptome .

< GPCR News < GPCRs in Oncology and Immunology Exacerbating effects of single-dose acute ethanol exposure The goal of this study is to determine the effects of single-dose acute ethanol exposure and GPR110 activation The GPR110 ligand synaptamide ameliorated this effect of ethanol by counteracting on the cAMP system,

< GPCR News < GPCRs in Oncology and Immunology The Effect of Cancer-Associated Mutations on Ligand Binding In this study, we aimed to investigate the effects of cancer patient-derived 5-HT2C receptor mutations This study shows that cancer-associated mutations of 5-HT2C receptor have diverse effects on ligand binding Such mutations may affect serotonin-mediated signaling in tumor cells as well as treatment strategies