Dr. GPCR Podcast << Back to podcast list Dr. G. Aditya Kumar About Dr. G. Aditya Kumar Dr. Aditya Kumar is a postdoctoral fellow at the University of Michigan Medical School. Aditya is interested in understanding the role of the membrane microenvironment in the subcellular organization, trafficking, and signaling of GPCRs. He received his Ph.D. from the Centre for Cellular and Molecular Biology at Hyderabad, India, where he studied the interaction of membrane cholesterol with the serotonin-1A receptor and its effects on receptor signaling and endocytosis. In addition, he explored the role of the host membrane in the entry of intracellular pathogens into macrophages. He currently uses high-resolution fluorescence microscopy and biochemistry to study GPCR trafficking mechanisms. In his (future) independent research career, Aditya aims to work at the interface of GPCR molecular pharmacology, subcellular trafficking, and membrane biology to better understand how the dynamic receptor microenvironment contributes to GPCR organization and function. Dr. G. Aditya Kumar on the web University of Michigan Puthenveedu Lab Google Scholar NIH ORCID LinkedIn Twitter Dr. GPCR Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

Dr. GPCR Podcast << Back to podcast list Dr. David Sykes About Dr. David Sykes " David Andrew Sykes, BSc Hons Pharmacology, MSc Molecular Biology and Biochemistry, PhD in Molecular Pharmacology & Drug Discovery. David has over 20+ years of experience working in a drug discovery environment mainly in a specialist assay development role and most recently with Novartis. In 2014 David joined the University of Nottingham and began a part-time PhD in Molecular Pharmacology and Drug Discovery that he was awarded in 2020. During this period David has made a significant contribution to the understanding of agonist/ antagonist GPCR kinetic determinants in an area of growing scientific interest. His current interests include the development of HTS fluorescence-based kinetic binding assays specifically designed to assess the kinetics of unlabelled compounds (and chemical fragments) and the use of purified receptor/ effector proteins as tools for drug discovery. " Dr. David Sykes on the web Veprintsev Lab ResearchGate LinkedIn Dr. GPCR Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

< GPCR News < GPCRs in Oncology and Immunology Chemokine Cxcl1-Cxcl2 heterodimer is a potent neutrophil chemoattractant Published date November 24, 2023 Abstract "Microbial infection is characterized by release of multiple proinflammatory chemokines that direct neutrophils to the insult site. How collective function of these chemokines orchestrates neutrophil recruitment is not known. Here, we characterized the role for heterodimer and show that the Cxcl1-Cxcl2 heterodimer is a potent neutrophil chemoattractant in mice and can recruit more neutrophils than the individual chemokines. Chemokine-mediated neutrophil recruitment is determined by Cxcr2 receptor signaling, Cxcr2 endocytosis, and binding to glycosaminoglycans. We have now determined heterodimer's Cxcr2 activity using cellular assays and Cxcr2 density in blood and recruited neutrophils in heterodimer-treated mice. We have shown that the heterodimer binds glycosaminoglycans with higher affinity and more efficiently than Cxcl1 or Cxcl2. These data collectively indicate that optimal glycosaminoglycan interactions and dampened receptor activity acting in concert in a dynamic fashion promote heterodimer-mediated robust neutrophil recruitment. We propose that this could play a critical role in combating infection." Authors Kirti V Sawant , Krishna Mohan Sepuru , Brigith Penaranda , Emily Lowry , Roberto P Garofalo , Krishna Rajarathnam Tags GPCR , heterodimer , inflammation , leukocyte , proteoglycan Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology Wnt pathway inhibition with the porcupine inhibitor LGK974 decreases trabecular bone but not fibrosis in a murine model with fibrotic bone Published date May 1, 2024 Abstract "G protein-coupled receptors (GPCRs) mediate a wide spectrum of physiological functions, including the development, remodeling, and repair of the skeleton. Fibrous dysplasia (FD) of the bone is characterized by fibrotic, expansile bone lesions caused by activating mutations in GNAS. There are no effective therapies for FD. We previously showed that ColI(2.3)+/Rs1+ mice, in which Gs-GPCR signaling was hyper-activated in osteoblastic cell lineages using an engineered receptor strategy, developed a fibrotic bone phenotype with trabecularization that could be reversed by normalizing Gs-GPCR signaling, suggesting that targeting the Gs-GPCR or components of the downstream signaling pathway could serve as a promising therapeutic strategy for FD. The Wnt signaling pathway has been implicated in the pathogenesis of FD-like bone, but the specific Wnts and which cells produce them remain largely unknown. Single-cell RNA sequencing on long-bone stromal cells of 9-wk-old male ColI(2.3)+/Rs1+ mice and littermate controls showed that fibroblastic stromal cells in ColI(2.3)+/Rs1+ mice were expanded. Multiple Wnt ligands were up- or downregulated in different cellular populations, including in non-osteoblastic cells. Treatment with the porcupine inhibitor LGK974, which blocks Wnt signaling broadly, induced partial resorption of the trabecular bone in the femurs of ColI(2.3)+/Rs1+ mice, but no significant changes in the craniofacial skeleton. Bone fibrosis remained evident after treatment. Notably, LGK974 caused significant bone loss in control mice. These results provide new insights into the role of Wnt and Gs-signaling in fibrosis and bone formation in a mouse model of Gs-GPCR pathway overactivation." Authors Hsuan Lung, Kelly L Wentworth, Tania Moody, Ariane Zamarioli, Apsara Ram, Gauri Ganesh, Misun Kang, Sunita Ho, Edward C Hsiao Tags Wnt pathway inhibition , fibrotic bone disease , fibrous dysplasia (FD) , osteoblasts , trabecular bone , G-protein coupled receptor signaling , GPCR , Gnas , Gsα . Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology Comparative Analysis of the GNAI Family Genes in Glioblastoma through Transcriptomics and Single-Cell Technologies Published date October 23, 2023 Abstract Glioblastoma multiforme (GBM) is one of the most aggressive cancers with a low overall survival rate. The treatment of GBM is challenging due to the presence of the blood-brain barrier (BBB), which hinders drug delivery. Invasive procedures alone are not effective at completely removing such tumors. Hence, identifying the crucial pathways and biomarkers for the treatment of GBM is of prime importance. We conducted this study to identify the pathways associated with GBM. We used The Cancer Genome Atlas (TCGA) GBM genomic dataset to identify differentially expressed genes (DEGs). We investigated the prognostic values of the guanine nucleotide-binding protein G(i) alpha subunit (GNAI) family of genes in GBM using a Chinese Glioma Genome Atlas (CGGA) dataset. Within this dataset, we observed the association in the tumor microenvironment between the gene expression of GNAI subunit 3 (GNAI3) and a poor prognosis. MetaCore and gene ontology (GO) analyses were conducted to explore the role of GNAI3 in co-expressed genes and associated signaling pathways using a transcript analysis. Notable pathways included "Cytoskeleton remodeling regulation of actin cytoskeleton organization by the kinase effectors of Rho GTPases" and "Immune response B cell antigen receptor (BCR) pathway". A single-cell analysis was used to assess GNAI3 expression in GBM. The results demonstrated that GNAI family genes, specifically GNAI3, were significantly associated with carcinogenesis and malignancy in GBM patients. Our findings suggest that the GNAI3 gene holds potential as a prognostic biomarker for GBM. Authors Ahmad Raza , Meng-Chi Yen , Gangga Anuraga , Iram Shahzadi , Muhammad Waqar Mazhar , Hoang Dang Khoa Ta , Do Thi Minh Xuan , Sanskriti Dey , Sachin Kumar , Adrian Wangsawijaya Santoso , Bianca Tobias William , Chih-Yang Wang Tags G-protein-coupled receptor (GPCR) , genome , glioblastoma , malignancy , molecular biomarker , prognosis , signaling pathway . Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology Structural Basis for the Recognition of GPRC5D by Talquetamab, a Bispecific Antibody for Multiple Myeloma Published date August 22, 2024 Abstract "Multiple myeloma (MM) is a complex hematological malignancy characterized by abnormal antibody production from plasma cells. Despite advances in the treatment, many patients experience disease relapse or become refractory to treatment. G-protein-coupled receptor class C group 5 member D (GPRC5D), an orphan GPCR predominantly expressed in MM cells, is emerging as a promising target for MM immunotherapy. Talquetamab, a Food and Drug Administration-approved T-cell-directing bispecific antibody developed for treatment of MM, targets GPRC5D. Here, we elucidate the structure of GPRC5D complexed with the Fab fragment of talquetamab, using cryo-electron microscopy, providing the basis for recognition of GPRC5D by the bispecific antibody. GPRC5D forms a symmetric homodimer with the interface between transmembrane helix (TM) 4 of one protomer and TM4/5 of the other protomer. A single talquetamab Fab interacts with the GPRC5D dimer with its orientation toward the dimer interface. All six complementarity-determining regions of talquetamab engage with extracellular loops and TM3/5/7. In particular, the side-chain of an arginine residue from the antibody penetrates into a shallow pocket on the extracellular surface of GPRC5D. The structure offers insights for optimizing antibody design against GPRC5D for relapsed or refractory MM therapy." Authors Jihong Jeong, Junhyeon Park, Geun Young Mo, Jinwoo Shin, Yunje Cho Tags GPRC5D , Multiple myeloma , class C GPCR , cryo-EM structure , talquetamab Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology Unbiased multitissue transcriptomic analysis reveals complex neuroendocrine regulatory networks mediated by spinal cord injury-induced immunodeficiency Published date September 30, 2023 Abstract "Background: Spinal cord injury (SCI), which causes loss of sensory and motor function in the body below the level of injury, is a devastating disease of the central nervous system. SCI leads to severe secondary immunosuppression, called SCI-induced immunodeficiency syndrome (SCI-IDS), which is characterized by increased susceptibility to infection and further exacerbates neurological dysfunction. Several studies have suggested that SCI-IDS is an independent risk factor for poor neurological prognosis. SCI-IDS predominantly occurs following injury above the T5 levels and eventually leads to systemic immune failure, possibly via the sympathetic-adrenal medullary axis and the hypothalamic‒pituitary‒adrenal (HPA) axis. However, the mechanism remains unclear. Methods and objectives: The concentrations of adrenocorticotropic hormone and cortisol in plasma, as well as changes in sympathetic activity (blood pressure and catecholamine levels in plasma), were assessed in rats in the high-level (T3) spinal cord injury (T3-SCI) group and the low-level (T10) spinal cord injury (T10-SCI) group. Second, the differential regulation of the gene network between the sympathetic-adrenal medullary axis and the HPA axis was explored by histology and multitissue transcriptomics, and the neuroendocrine-immune network associated with SCI-IDS was further elucidated. Results: The spleen and thymus gland, which are secondary immune organs, were significantly atrophied in rats in the T3-SCI group, and the white pulp of the spleen was significantly atrophied. The level of cortisol, which is mediated by the adrenal glands, was markedly elevated, but norepinephrine levels were markedly decreased. There was no difference in adrenocorticotropic hormone expression between any of the groups. The transcriptome analysis results showed that the downregulated differentially expressed genes (DEGs) in the T3-SCI group were enriched in the GO term immunoregulation, indicating that splenic immune function was markedly impaired after high-level SCI. The upregulated DEGs in the hypothalamus (hub genes: Nod2, Serpine1, Cebpb, Nfkbil1, Ripk2, Zfp36, Traf6, Akap8, Gfer, Cxcl10, Tnfaip3, Icam1, Fcgr2b, Ager, Dusp10, and Mapkapk2) were significantly enriched in inflammatory pathways, and the downregulated genes (hub genes: Grm4, Nmu, P2ry12, rt1-bb1, Oprm1, Zfhx2, Gpr83, and Chrm2) were enriched in pathways related to inhibitory Gi-mediated G protein-coupled receptor (Gi-GPCR) neurons and neuropeptide changes. The upregulated genes in the adrenal glands (hub genes: Ciart, per2, per3, cry1, and cry2) were enriched in cortisol secretion and circadian rhythm changes, and the downregulated genes (hub genes: IL7r, rt1-bb, rt1-bb1, rt1-da, rt1-ba, cd74, cxcr3, vcam1, ccl5, bin1, and IL8) were significantly enriched in MHC-mediated immune responses. Conclusions: To explore the possible mechanism underlying SCI-IDS, this study assessed the differential regulation of the gene network associated with neuroendocrine immunity after SCI. Progressive neuroinflammation spreads after injury, and neurotransmission through Gi-mediated G protein-coupled receptors in the HPA axis and neuropeptide production by the hypothalamus are inhibited. Disruption of the connection between the hypothalamus and the adrenal glands causes autonomous regulation of the adrenal glands, disturbance of circadian rhythm and finally hypercortisolemia, leading to general suppression of peripheral adaptive immunity. Neuraxial nerve inflammation caused by SCI persists indefinitely, blocking nerve repair; persistent system-wide immunosuppression in the periphery results in increased susceptibility to infection, leading to poor neurological prognosis." Authors Hong Zeng , Li Cheng , De-Zhi Lu , Shuai Fan , Ke-Xin Wang , Li-Li Xu , Bin Cai , Mou-Wang Zhou , Jin-Wu Wang Tags Hypothalamo-pituitary-adrenal axis , Neuroendocrine immunomodulatory axis , Neuroinflammation , SCI-induced immunodeficiency syndrome , Transcriptome Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

Full Agenda Adhesion GPCR workshop 2024 CINVESTAV, Mexico City, Mexico October 23-25 Download PDF Program HERE < Back to Full Agenda Posters Interrogating The Role Of CELSR1 (ADGRC1) In Breast Cancer Caroline Formstone Generation and characterization of collecting duct specific GPR56 knockout mice Jianxiang Xue Anti-Tumorigenic Role of Brain Angiogenesis Inhibitor 3 (BAI3) in WNT-Activated Medulloblastomas Virginea de Araujo Farias Conformational And Functional Coupling Between Extracellular and Transmembrane Regions of a Holo-Adhesion GPCR Szymon P. Kordon Deorphanization Of The Adhesion GPCRs GPR110 and GPR116 Tingzhen Shen Self-Cleavage of GPR110 SEA Domain and Its Impact on GAIN Domain Autoproteolysis Bill Huang Tethered Agonist Dependent ADGRL3 Signaling Activity In The G12/13 Pathway Júlia Rosell Endocytic Cues Determine the Signaling Profile of Adhesion GPCR ADGRL1 / Latrophilin-1 Sheila Ribalta-Mena GPR110 modulates anxiety-like behaviors and memory function in mice potentially through neuronal and neuroimmune alterations during neurodevelopment Mariam Melkumyan Interrogating The Role Of CELSR1 (ADGRC1) In Breast Cancer Caroline Formstone Abstract "Breast cancer is the most common form of cancer amongst women. Ductal carcinomas are increasingly diagnosed but identifying which will progress to invasive disease remains difficult highlighting an urgent need for new biomarkers that distinguish ductal carcinomas on this basis. Planar cell polarity (PCP) proteins contribute to tumour growth and invasion. Recent studies identify CELSR1, a key PCP gene, as a novel biomarker for early-stage breast cancer. CELSR1 is reactivated in luminal-type ductal carcinomas. The impact of CELSR1 on cancer progression, however, is unclear. Our working hypothesis is that distinct CELSR1 protein isoforms differentially regulate tissue adhesiveness by influencing the stability/plasticity of cell-cell and cell-matrix contacts. Notably, our pilot data from luminal-type breast cancer cell lines representative of breast carcinomas with lower versus higher invasive potential reveal differential enrichment of CELSR1 protein isoforms. To test the specific hypothesis that biased expression of CELSR1 isoforms will predict invasive potential of a luminal breast carcinoma we will (a) determine, via loss-of-function assays in vitro and in vivo, whether CELSR1 protein isoforms differentially influence the stability of cell-cell and/or cell-matrix adhesions to dictate breast tumour invasive mechanism (b) quantify CELSR1 isoform expression (mRNA and protein) within patient luminal carcinoma samples exhibiting non-invasive or invasive features, the latter including heterogeneous tumours with mixed pathology. Through study of known protein isoforms of CELSR1, which would be missed in gene expression microarray analyses, we hope to illuminate the prognostic potential of CELSR1 for early-stage breast cancer." Authors & Affiliations "Klena, Ladislav University of Hertfordshire" About Caroline Formstone "Cell and developmental biologist with a focus on how planar cell polarity drives complex tissue morphogenesis. I study the cell and tissue level consequences of its failure in foetal development and of its reemployment in cancer" Caroline Formstone on the web University of Hertfordshire Generation and characterization of collecting duct specific GPR56 knockout mice Jianxiang Xue Abstract "GPR56 is a multifunctional adhesin G protein-coupled receptor involved in diverse biological processes. The role of GPR56 in the kidneys has been understudied. A recent study demonstrated that GPR56 in the glomerular endothelial cells promoted diabetic kidney disease progression via regulation of eNOS. Using RNAscope in situ hybridization (ISH) for GPR56, aquaporin 2 and NKCC2 (thick ascending limb, TAL marker), we detected GPR56 mRNA highly expressed in the collecting duct and TAL of the loop of Henle with limited expression in the proximal tubule. To determine the physiological role of GPR56 in the collecting duct, we generated a collecting duct-specific GPR56 knockout (GPR56CD-KO) mouse model by crossing GPR56flox (Control) with cadherin 16 Cre mice. The deletion of GPR56 in the collecting duct was confirmed by RNAscope ISH. GPR56CD-KO mice were born at predicted Mendelian frequencies, appeared grossly indistinguishable from Con mice, and developed normally. For baseline phenotypic characterization, blood gas analysis showed no differences in blood pH, blood HCO3-, blood Na+, or blood K+ between GPR56CD-KO and control mice. Metabolic cage experiments demonstrated no differences in fluid intake, urine volume, urinary pH or urine osmolality between genotypes in baseline. 24hr water deprivation experiment showed that GPR56CD-KO mice can concentrate urine as effectively as control mice. In conclusion, we successfully generated collecting duct-specific GPR56 knockout mouse and found no defective urine concentrating ability in GPR56CD-KO mice. This mouse model will be useful to delineate the collecting duct-specific role of GPR56 for renal function, including acid-base regulation." Authors & Affiliations "Hailey Steichen, Krystin Eaton, Teagan Yan, and Nathan Zaidman; Department of Biochemistry and Molecular Biology, University of New Mexico" About Jianxiang Xue "I am a postdoctoral researcher working in the Department of Biochemistry and Molecular Biology, University of New Mexico. I earned my PhD degree in Biomedical Sciences from the University of South Florida. During my graduate studies, using various transgenic mouse models and expertise in intestinal and renal physiology, I systematically characterized the function of sodium/hydrogen exchanger 3 in the intestine and kidneys for fluid and electrolyte homeostasis and acid-base balance. My predoctoral work was supported by an American Heart Association fellowship. Since staring my postdoctoral training, I have continued to develop my expertise to answer fundamental questions on adhesion GPCR in renal physiology and pathology. In my free time, I enjoy reading, workouts, and hiking." Jianxiang Xue on the web Zaidman Physiology Lab Anti-Tumorigenic Role of Brain Angiogenesis Inhibitor 3 (BAI3) in WNT-Activated Medulloblastomas Virginea de Araujo Farias Abstract Only available for AGPCR 24 Workshop Attendees Authors & Affiliations "Van Meir, Erwin G. University of Alabama at Birmingham" About Virginea de Araujo Farias "Brain Angiogenesis Inhibitor (BAI) proteins are members of group VII of the adhesion G protein-coupled receptor (aGPCR) family. BAI1-3 are highly expressed in the brain, where they participate in synaptogenesis and synapse maintenance. In cancers, BAI1-3 expression can be lost through epigenetic silencing, copy number loss or truncating mutations. In medulloblastomas (MB), BAI3 (ADGRB3) expression is specifically reduced in the WNT-activated group (WNT-MB), but not in the other three molecular groups. WNT pathway activation in WNT-MB is driven by mutations of the CTNNB1 gene, activating ß-catenin-dependent signaling; however, no interactions between BAI3 and the WNT signaling pathway have been described so far. MAGI3, a PDZ-containing scaffolding protein is known to downregulate WNT signaling by interacting with ß-catenin in gliomas, but it is unknown whether this involves BAI3. To explore a possible connection between BAI3 and ß-catenin signaling through MAGI3 in WNT-MB, we probed for potential protein-protein interactions using co-IP experiments. We found an interaction between BAI3 and MAGI3 in mouse brain lysates. Therefore, we hypothesize that re-expression of BAI3 in WNT-MB cells will restrain ß-catenin activity through the formation of a BAI3/MAGI3/ß-catenin complex, reducing their tumorigenic properties. To test this hypothesis, we created WNT-like MB cell lines stably expressing tet-on wild-type BAI3 or a BAI3 lacking the C-terminal PDZ-binding motif (PBM). We will present the effects of BAI3 re-expression on WNT-MB cells oncogenic properties and signaling." Virginea de Araujo Farias on the web Google Scholar Conformational And Functional Coupling Between Extracellular and Transmembrane Regions of a Holo-Adhesion GPCR Szymon P. Kordon Abstract "Adhesion G Protein-Coupled Receptors (aGPCRs) are key cell-adhesion molecules involved in numerous physiological functions. aGPCRs have large multi-domain extracellular regions (ECR) that mediate cell adhesion and play roles in transmitting extracellular signals to the inside of the cell. Ligand binding and mechanical force applied on the ECR regulate receptor function. However, how the ECR communicates with the seven-pass transmembrane domain (7TM) remains elusive, because the relative orientation and dynamics of the ECR and 7TM within a holoreceptor is unclear. Here, we describe the cryo-EM reconstruction of an aGPCR, Latrophilin3/ADGRL3, and reveal that the conserved GAIN domain, that directly precedes 7TM, adopts a parallel orientation to the membrane and has constrained movement. Single-molecule FRET experiments unveil three slow-exchanging FRET states of the ECR relative to the 7TM within the holoreceptor. GAIN-targeted antibodies, and cancer-associated mutations at the GAIN-7TM interface, alter holoreceptor conformations, and modulate downstream receptor signaling. Altogether, this data demonstrates conformational and functional coupling between the ECR and 7TM, suggesting an ECR-mediated mechanism for aGPCR activation." Authors & Affiliations "Cechova Kristina (3), Bandekar Sumit J.(1, 2), Leon Katherine (1, 2), Dutka Przemysław (1, 4), Siffer Gracie (3), Kossiakoff Anthony A. (1), Vafabakhsh Reza (3), Araç Demet (1, 2) 1. Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA; 2. Neuroscience Institute, Institute for Biophysical Dynamics, and Center for Mechanical Excitability, The University of Chicago, Chicago, IL, USA; 3. Department of Molecular Biosciences, Northwestern University, Evanston, IL, USA; 4. Current affiliation: Department of Structural Biology, Genentech, South San Francisco, CA, USA" About Szymon P. Kordon "I am a postdoctoral scholar in the Araç Lab at The University of Chicago, studying the structure and function of aGPCRs. Utilizing synthetic antibody fragments, I aim to understand better the structural basis of the aGPCRs activation and signaling and to characterize ECR-mediated signal transduction at the molecular level." Szymon P. Kordon on the web Araç Laboratory at UChicago Deorphanization Of The Adhesion GPCRs GPR110 and GPR116 Tingzhen Shen Abstract Only available for AGPCR 24 Workshop Attendees Authors & Affiliations "Frank E. Kwarcinski, Gregory G. Tall (University of Michigan, Ann Arbor)" About Tingzhen Shen "A graduate student from Tall Lab, department of Pharmacology, University of Michigan, Ann Arbor." Tingzhen Shen on the web University of Michigan Self-Cleavage of GPR110 SEA Domain and Its Impact on GAIN Domain Autoproteolysis Bill Huang Abstract Only available for AGPCR 24 Workshop Attendees Authors & Affiliations "Hee-Yong Kim, Laboratory of Molecular Signaling, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA" About Bill Huang "Researcher" Bill Huang on the web LinkedIn Tethered Agonist Dependent ADGRL3 Signaling Activity In The G12/13 Pathway Júlia Rosell Abstract Only available for AGPCR 24 Workshop Attendees Authors & Affiliations "Regmi, Rajesh (1), Perry-Hauser, Nicole A. (2), Javitch, Jonathan A. (2), Mathiasen, Signe (1) (1) Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. (2) Department of Psychiatry and Molecular Pharmacology and Therapeutics, Columbia University Vagelos College of Physicians and Surgeons, New York, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, USA" About Júlia Rosell "I am a first-year PhD student with two years of experience in the adhesion GPCR field. I completed my Master’s thesis on ADGRL3, where I conducted research involving mammalian cell cultures and techniques such as BRET assays and gene expression assays. Currently, my research focuses on the intracellular signaling of ADGRL3 from a single-molecule perspective and investigating how the binding of extracellular transsynaptic ligands modulates ADGRL3 activity, aiming to elucidate their interplay." Júlia Rosell on the web LinkedIn Endocytic Cues Determine the Signaling Profile of Adhesion GPCR ADGRL1 / Latrophilin-1 Sheila Ribalta-Mena Abstract Only available for AGPCR 24 Workshop Attendees Authors & Affiliations " Hernández-Aranda Judith 2, Correoso-Braña Kerlys 1, Vialou Vincent 3, Leduc Richard 4, Olivares-Reyes Jesús Alberto 2, Boucard Antony A1. 1 Department of Cell Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav-IPN), México City, México. 2 Department of Biochemistry, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav-IPN), México City, México. 3 Sorbonne Université, Inserm, CNRS, Neurosciences Paris Seine, Paris, France. 4 Department of Physiology and Pharmacology, Université de Sherbrooke, Sherbrooke, Canada " About Sheila Ribalta-Mena " Cell Biology PhD student " Sheila Ribalta-Mena on the web CINVESTAV ResearchGate LinkedIn GPR110 modulates anxiety-like behaviors and memory function in mice potentially through neuronal and neuroimmune alterations during neurodevelopment Mariam Melkumyan Abstract "GPR110, an adhesion G protein coupled receptor (GPCR), is widely expressed in developing brains but diminishes in adult stage except in the hippocampus, a region involved in learning and memory. Ligand-induced GPR110 signaling stimulates neurogenesis and synaptogenesis during development, and the absence of the ligand-induced signaling causes object recognition and spatial memory deficits in adulthood and increased neuroinflammatory responses. Nevertheless, the role of GPR110 signaling in behavioral consequences has not been fully explored. This study aimed to understand the effects of GPR110 on mouse behaviors in relation to neurodevelopmental and neuroimmune gene and protein expression. Anxiety and memory function were tested using both male and female mice at 5-6 month of age. GPR110 knockout (KO) mice displayed trends for increased anxiety-like behaviors in the elevated plus maze test and in the open field test. Memory tests, including the novel object test and the radial 8-arm maze showed worsened spatial and reference memory in the GPR110 KO mice compared to wildtype mice. The y-maze showed a significant sex by genotype interactions with GPR110 KO male mice having increased number of correct alterations and errors, while the GPR110 KO females had fewer correct alterations and errors. RNAseq data indicated significantly impaired developmental gene expression for neuronal differentiation, axonogenesis, and synaptogenesis, as well as altered neuroinflammatory marker expression in GPR110 KO mouse brains. Further studies exploring the protein expression and neural activity of these mouse brain will give insight on the mechanism underlying the behavioral consequences associated with the GPR110 receptor. " Authors & Affiliations "Joel Toro, Bill Huang, Hee-Yong Kim Laboratory of Molecular Signaling, National Institute of Alcohol Abuse and Alcoholism, NIH" About Mariam Melkumyan "Mariam Melkumyan is a postdoctoral fellow at the Laboratory of Molecular Signaling studying the role of GPR110 in neurotransmission and neuroimmune activity involved in learning and memory, anxiety, and alcohol use. Mariam, originally from Armenia, completed her bachelor's degree in Neuroscience at American University in Washington, DC and her dual-title PhD in Neuroscience and Clinical and Translational Sciences at Penn State College of Medicine in Hershey, PA. Mariam started her postdoctoral training in February 2024 and is hoping to become an academic professor and mentor the next generation of scientists." Mariam Melkumyan on the web LinkedIn Google Scholar < Previous Session Next Session >

< GPCR News < GPCRs in Oncology and Immunology Increased protease-activated receptor 1 autoantibodies are associated with severe COVID-19 Published date December 27, 2022 Abstract In patients with severe #COVID19 , increased levels of autoantibodies against PAR1 were found. These might serve as allosteric agonists of PAR1 on endothelial cells and platelets, and thus might contribute to the pathogenesis of microthrombosis in COVID-19. Authors Florian Tran , Danielle M M Harris , Alena Scharmacher , Hanna Graßhoff , Kristina Sterner , Susanne Schinke , Nadja Käding , Jens Y Humrich , Otávio Cabral-Marques , Joana P Bernardes , Neha Mishra , Thomas Bahmer , Jeanette Franzenburg , Bimba F Hoyer , Andreas Glück , Martina Guggeis , Alexander Ossysek , Andre Küller , Derk Frank , Christoph Lange , Jan Rupp , Jan Heyckendorf , Karoline I Gaede , Howard Amital , Philip Rosenstiel , Yehuda Shoenfeld , Gilad Halpert , Avi Z Rosenberg , Kai Schulze-Forster , Harald Heidecke , Gabriela Riemekasten , Stefan Schreiber . Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology Minireview: functional roles of tissue kallikrein, kinins, and kallikrein-related peptidases in lung cancer Published date July 3, 2023 Abstract "Despite campaigns and improvements in detection and treatment, lung cancer continues to increase worldwide and represents a major public health problem. One approach to treating patients suffering from lung cancer is to target surface receptors overexpressed on tumor cells, such as GPCR-family kinin receptors, and proteases that control tumor progression, such as kallikrein-related peptidases (KLKs). These proteases have been visualized in recent years due to their contribution to the progression of cancers, such as prostate and ovarian cancer, facilitating the invasive and metastatic capacity of tumor cells in these tissues. In fact, KLK3 is the specific prostate antigen, the only tissue-specific biomarker used to diagnose this malignancy. In lung cancer to date, evidence indicates that KLK5, KLK6, KLK8, KLK11, and KLK14 are the major peptidases regulated and involved in its progression. The expression levels of KLKs in this neoplasm are modulated by the secretome of the different cell types present in the tumor microenvironment, the cancer subtype and the tumor stage, among others. Considering the multiple functions of kinin receptors and KLKs, this review highlights their roles, even considering the SARS-CoV-2 effects. Since lung cancer is often diagnosed in advanced stages, our efforts should focus on early diagnosis, validating for example specific KLKs, especially in high-risk populations such as smokers and people exposed to carcinogenic fumes, oil fields, and contaminated workplaces, unexplored fields to investigate. Furthermore, their modulation could be considered as a promising approach in lung cancer therapeutics." Authors Adriana Stuardo-Parada , Rodrigo López-Muñoz , Franz Villarroel-Espindola , Carlos D Figueroa , Pamela Ehrenfeld Tags KLKs , Kallikrein-related peptidases , Kinin receptors , Kinins , Lung cancer , SARS-CoV-2 Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

Retreat 2023 About Program Registration Logo Contest Committee Sponsors GPCR Retreat Program < Back to schedule Interaction with the cell adhesion molecule NEGR1 affects mGluR5 cell signalling Date & Time Friday, November 3rd / 1:30 PM Abstract Coming Soon About Fabiola Ribeiro "Fabiola M. Ribeiro is an Associate Professor at the Universidade Federal de Minas Gerais (UFMG). She obtained her Ph.D. from UFMG in 2006 and, after that, she performed her postdoctorate studies at the University of Western Ontario, London, Canada, under Dr. Stephen Ferguson’s supervision. She returned to Brazil in 2010, when she founded her independent research group. Since then, Dr. Ribeiro has supervised eleven M.Sc. and six Ph.D. students, as well as five post-doctorate fellows. Nowadays, her research group comprises four undergraduates, two M.Sc., and six Ph.D. students, as well as five post-doctorate fellows and a lab technician. Dr. Ribeiro has 86 per reviewed scientific papers published in highly respected scientific journals, including 17 papers published in journals with impact higher than 7. Moreover, Dr. Ribeiro is the first or last author of 33 of these published articles. Dr. Ribeiro H factor is 28, according to Web of Science, and she is an affiliated member of the Brazilian Academy of Science. She was able to have several grants approved in Brazil and abroad, which have granted her research group a laboratory containing all the necessary equipment to perform state-of-the-art technologies. Dr. Ribeiro main scientific contributions include the study of the mechanisms involved in neurodegeneration and the characterization of neuroprotective drugs acting on the glutamatergic system. These drugs were shown to be very effective to rescue the cell death observed in a mouse model of Huntington’s disease (HD), decreasing synaptic loss and enhancing HD related memory impairment." Fabiola Ribeiro on the web Federal University of Minas Gerais, Brazil Pubmed ResearchGate Instagram Dr. GPCR Previous Event Next Event Great Lakes GPCR Retreat and Club des Récepteurs à Sept Domaines Transmembranaires du Québec Great Lakes GPCR Retreat and Club des Récepteurs à Sept Domaines Transmembranaires du Québec 22nd GPCR Retreat Sponsored by

Dr. GPCR Podcast << Back to podcast list Dr. Demet Araç About Dr. Demet Araç "Demet was an undergraduate at Bilkent University in Turkey, where she majored in Molecular Biology and Genetics. She moved to the University of Texas Southwestern Medical Center at Dallas in 2000 to work with Dr. Jose Rizo-Rey as a graduate student to elucidate the mechanisms of neurotransmitter release. After finishing her graduate training, she joined Dr. Axel Brunger’s lab at Stanford University to study the structure and function of cell-adhesion proteins at the synapse. In 2013, Demet began her independent research career at the University of Chicago within the Department of Biochemistry and Molecular Biology." Dr. Demet Araç on the web University of Chicago Araç Laboratory Google Scholar Twitter Dr. GPCR AI Summary AI-generated content may be inaccurate or misleading. Always check for accuracy. Quick recap Yamina and Demet discussed their personal backgrounds, academic backgrounds, and career paths, with a focus on their experiences in the field of GPCR (G protein-coupled receptor). Demet shared his journey of studying adhesion GPCRs, the challenges he faced, and the progress made in understanding their structure and function. They also discussed the ongoing developments in the GPCR field, the upcoming adhesion GPCR consortium meeting, and the naming conventions of proteins in the field. Lastly, they shared their views on pursuing one's passions and not being afraid of the unknown, and Demet expressed his satisfaction with his first podcast experience. Next steps • Yamina will send an email to Demet, encouraging him to distribute information about the Doctor GPCR Symposium to his team, including students, postdocs, and PhD students, and will share the recording of the podcast with Demet for the same purpose. • Demet will distribute information about the Doctor GPCR Symposium to his team and encourage his students, postdocs, and PhD students to contact Yamina for potential speaking opportunities at the symposium or other events. Summary Personal Backgrounds and GPCR Interest Yamina and Demet had a discussion about their personal backgrounds, interests, and experiences. Yamina shared her experiences of living in different countries and the adaptability skills it required. Demet, who had studied various subjects including chemistry, physics, biology, and math, shared his interest in science and physics. He also opened up about his childhood experiences of living in a place with limited pedestrian infrastructure. Yamina inquired about Demet's interest in studying GPCRs, and he explained his motivation stemmed from his experiences as an international student. They also acknowledged the cultural differences between Demet's home country, Turkey, and Yamina's, Canada. Academic Backgrounds and Career Paths Discussion Demet and Yamina discussed their academic backgrounds and career paths, with a focus on their experiences in academia. Demet shared that his interest in science led him to study biology, genetics, and molecular biophysics in Turkey and the United States, eventually becoming a professor at UT Southwestern Medical Center in Dallas. Yamina asked about Demet's career aspirations, to which he responded that he pursued science because he enjoyed it. They also discussed their scientific journeys, focusing on their work on adhesion GPCRs, a field that was largely neglected at the time. Demet's research on the gain domain of adhesion GPCRs started during his postdoctoral studies and continued into his faculty position, despite initial challenges in securing funding. Demet's Journey in Studying Adhesion GPCRs Demet discussed his journey in studying adhesion GPCRs, outlining his collaborations, challenges, and the progress made in understanding their structure and function. He explained that initially, the field lacked adequate tools, and his lab had to develop new techniques to work with these complex proteins. Over the years, Demet's team expanded their collaborations and improved their understanding of the GPCRs through various approaches, including structural biology and signaling assays. Yamina expressed her appreciation for Demet's work and asked about the development of the GPCR field over time. Demet explained that since the year 2000, the field has seen significant growth, with important discoveries such as the transmembrane region structures mediated by agonists. GPCR Field and Naming Convention Discussion Demet and Yamina discussed the ongoing developments in the GPCR field and the upcoming adhesion GPCR consortium meeting, which Anthony will be organizing in Mexico in October. They also addressed the naming conventions of proteins in the field, with Yamina expressing concern about the potential confusion caused by changes in nomenclature. Lastly, they shared their preferences for GPCRs, with Demet expressing a particular fondness for certain adhesion GPCRs. GPCR Field Progress and Advice for Junior Scientists Demet and Yamina discussed the progress of their research in the GPCR (G protein-coupled receptor) field, specifically focusing on adhesion GPCRs. Demet shared that they have been working on the Latrophilin project since 2013, screening about 20 adhesion GPCRs, with the Latrophilin 3 construct proving most successful. They also discussed the importance of the extracellular region of these receptors and its potential as a drug target. Demet highlighted a series of realizations over the years about the importance of the GPCR field and its applications, emphasizing that it's not just about one "Aha!" moment. Yamina expressed her love for the GPCR field and asked for advice for junior scientists interested in the same. Embracing Passions and Embracing Unknowns Demet and Yamina discussed the importance of pursuing one's passions and not being afraid of the unknown in their chosen fields. Demet shared his belief that he was driven by a biological need to tackle more challenging tasks. Both agreed that one should find work exciting and interesting, as life is too short to spend doing things one doesn't enjoy. Yamina posed the question of what advice Demet would give his younger self, but Demet responded that he wouldn't change his past actions, as he believed they led him to his current fulfilling path. Podcast Experience and Upcoming Collaboration Demet expressed satisfaction about his first podcast experience and showed interest in sharing his insights in future episodes. Yamina shared her plans for an upcoming Doctor GPCR Symposium in June, for which Demet is the first confirmed speaker, and discussed potential challenges and solutions. The conversation ended with an agreement to collaborate in the future, with Yamina expressing her intention to reach out to Demet's students and postdocs for potential podcast participation. Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

< GPCR News < GPCRs in Oncology and Immunology Comparison of infectious complications with BCMA-directed therapies in multiple myeloma Published date May 31, 2024 Abstract "B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade ≥3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively). Comparing T-cell redirecting therapies, the incidence rate of severe infections was significantly lower with CAR-T compared to BsAb at 1-year (incidence-rate-ratio [IRR] = 0.43, 95%CI 0.25-0.76, P = 0.004). During periods of treatment-emergent hypogammaglobulinemia, BsAb recipients had higher infection rates (IRR:2.27, 1.31-3.98, P = 0.004) and time to severe infection (HR 2.04, 1.05-3.96, P = 0.036) than their CAR-T counterparts. During periods of non-neutropenia, CAR-T recipients had a lower risk (HR 0.44, 95%CI 0.21-0.93, P = 0.032) and incidence rate (IRR:0.32, 95% 0.17-0.59, P < 0.001) of severe infections than BsAb. In conclusion, we observed an overall higher and more persistent risk of severe infections with BsAb. Our results also suggest a higher infection risk during periods of hypogammaglobulinemia with BsAb, and with neutropenia in CAR-T recipients." Authors Karthik Nath, Tala Shekarkhand, David Nemirovsky, Andriy Derkach, Bruno Almeida Costa, Noriko Nishimura, Tasmin Farzana, Colin Rueda, David J Chung, Heather J Landau, Oscar B Lahoud, Michael Scordo, Gunjan L Shah, Hani Hassoun, Kylee Maclachlan, Neha Korde, Urvi A Shah, Carlyn Rose Tan, Malin Hultcrantz, Sergio A Giralt, Saad Z Usmani, Zainab Shahid, Sham Mailankody, Alexander M Lesokhin Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology Stable Binding of Full-Length Chemerin is Driven by Negative Charges in the CMKLR1 N-terminus Published date May 13, 2023 Abstract "The adipokine chemerin is the endogenous ligand of the chemokine-like receptor 1 (CMKLR1), a member of the family of G protein-coupled receptors (GPCR). This protein ligand plays an important role in obesity and inflammatory processes. Stable receptor-ligand interactions are highly relevant for its different physiological effects, e. g. the migration of immune cells towards sites of inflammation. Here, we demonstrate that negative charges in the CMKLR1 N-terminus are involved in the formation of strong contacts with a specific positively charged patch at the surface of full-length chemerin, which is absent in the short nonapeptide agonist chemerin-9 explaining its reduced affinity. Using receptor chimera of G protein-coupled receptor 1 (GPR1) and CMKLR1, we were able to identify the residues of this interaction and its relevance for stable full-length chemerin binding. This may help to develop more potent ligands for the treatment of inflammatory related diseases." Authors Kevin Kretschmer , Tristan Zellmann , Karin Mörl , Annette G Beck-Sickinger . Tags double mutant cycle analysis , protein expression , protein-protein interaction , receptor binding , signal transduction . Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology Dynamic Phosphoproteomics of BRS3 Activation Reveals the Hippo Signaling Pathway for Cell Migration Published date June 25, 2023 Abstract "Bombesin receptor subtype-3 (BRS3) is an orphan G-protein coupled receptor (GPCR) that is involved in a variety of pathological and physiological processes, while its biological functions and underlying regulatory mechanisms remain largely unknown. In this study, a quantitative phosphoproteomics approach was employed to comprehensively decipher the signal transductions that occurred upon intracellular BRS3 activation. The lung cancer cell line H1299-BRS3 was treated with MK-5046, an agonist of BRS3, for different durations. Harvested cellular proteins were digested and phosphopeptides were enriched by immobilized titanium (IV) ion affinity chromatography (Ti4+-IMAC) for label-free quantification (LFQ) analysis. A total of 11,938 phosphopeptides were identified, corresponding to 3,430 phosphoproteins and 10,820 phosphosites. Data analysis revealed that 27 phosphopeptides corresponding to six proteins were involved in the Hippo signaling pathway, which was significantly regulated by BRS3 activation. Verification experiments demonstrated that downregulation of the Hippo signaling pathway caused by BRS3 activation could induce the dephosphorylation and nucleus localization of the Yes-associated protein (YAP), and its association with cell migration was further confirmed by kinase inhibition. Our data collectively demonstrate that BRS3 activation contributes to cell migration through downregulation of the Hippo signaling pathway." Authors Miao Guo , Yan Zhang , Lehao Wu , Ye Sheng , Jiaqi Zhao , Zeyuan Wang , Huiyu Wang , Lu Zhang , Hua Xiao Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology A disturbed metabolite-GPCR axis is associated with microbial dysbiosis in IBD patients: Potential role of GPR109A in macrophages Published date September 2, 2024 Abstract "Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by disrupted immune function. Indeed, gut microbiota dysbiosis and metabolomic profile alterations, are hallmarks of IBD. In this scenario, metabolite-sensing G-protein coupled receptors (GPCRs), involved in several biological processes, have emerged as pivotal players in the pathophysiology of IBD. The aim of this study was to characterize the axis microbiota-metabolite-GPCR in intestinal surgical resections from IBD patients. Results showed that UC patients had a lower microbiota richness and bacterial load, with a higher proportion of the genus Cellulosimicrobium and a reduced proportion of Escherichia, whereas CD patients showed a decreased abundance of Enterococcus. Furthermore, metabolomic analysis revealed alterations in carboxylic acids, fatty acids, and amino acids in UC and CD samples. These patients also exhibited upregulated expression of most metabolite-sensing GPCRs analysed, which positively correlated with pro-inflammatory and pro-fibrotic markers. The role of GPR109A was studied in depth and increased expression of this receptor was detected in epithelial cells and cells from lamina propria, including CD68+ macrophages, in IBD patients. The treatment with β-hydroxybutyrate increased gene expression of GPR109A, CD86, IL1B and NOS2 in U937-derived macrophages. Besides, when GPR109A was transiently silenced, the mRNA expression and secretion of IL-1β, IL-6 and TNF-α were impaired in M1 macrophages. Finally, the secretome from siGPR109A M1 macrophages reduced the gene and protein expression of COL1A1 and COL3A1 in intestinal fibroblasts. A better understanding of metabolite-sensing GPCRs, such as GPR109A, could establish their potential as therapeutic targets for managing IBD." Authors Cristina Bauset, Miguel Carda-Diéguez, Andrea Cejudo-Garcés, Elena Buetas, Marta Seco-Cervera, Dulce Carolina Macias-Ceja, Francisco Navarro-Vicente, Juan Vicente Esplugues, Sara Calatayud, Álex Mira, Dolores Ortiz-Masiá, María Dolores Barrachina, Jesús Cosín-Roger Tags GPR109A , IBD , Metabolite-sensing GPCRs , Metabolomic alterations , Microbiota dysbiosis , Pro-inflammatory macrophages Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology Interplay between G protein-coupled receptors and nanotechnology Published date July 28, 2023 Abstract "G protein-coupled receptors (GPCRs), as the largest family of membrane receptors, actively modulate plasma membrane and endosomal signalling. Importantly, GPCRs are naturally nanosized, and spontaneously formed nanoaggregates of GPCRs (natural nano-GPCRs) may enhance GPCR-related signalling and functions. Although GPCRs are the molecular targets of the majority of marketed drugs, the poor pharmacokinetics and physicochemical properties of GPCR ligands greatly limit their clinical applicability. Nanotechnology, as versatile techniques, can encapsulate GPCR ligands to assemble synthetic nano-GPCRs to overcome their obstacles, robustly elevating drug efficacy and safety. Moreover, endosomal delivery of GPCR ligands by nanoparticles can precisely initiate sustained endosomal signal transduction, while nanotechnology has been widely utilized for isolation, diagnosis, and detection of GPCRs. In turn, due to overexpression of GPCRs on the surface of various types of cells, GPCR ligands can endow nanoparticles with active targeting capacity for specific cells via ligand-receptor binding and mediate receptor-dependent endocytosis of nanoparticles. This significantly enhances the potency of nanoparticle delivery systems. Therefore, emerging evidence has revealed the interplay between GPCRs and nanoparticles, although investigations into their relationship have been inadequate. This review aims to summarize the interaction between GPCRs and nanotechnology for understanding their mutual influences and utilizing their interplay for biomedical applications. It will provide a fundamental platform for developing powerful and safe GPCR-targeted drugs and nanoparticle systems. STATEMENT OF SIGNIFICANCE: GPCRs as molecular targets for the majority of marketed drugs are naturally nanosized, and even spontaneously form nano aggregations (nano-GPCRs). Nanotechnology has also been applied to construct synthetic nano-GPCRs or detect GPCRs, while endosomal delivery of GPCR ligands by nanoparticles can magnify endosomal signalling. Meanwhile, molecular engineering of nanoparticles with GPCRs or their ligands can modulate membrane binding and endocytosis, powerfully improving the efficacy of nanoparticle system. However, there are rare summaries on the interaction between GPCRs and nanoparticles. This review will not only provide a versatile platform for utilizing nanoparticles to modulate or detect GPCRs, but also facilitate better understanding of the designated value of GPCRs for molecular engineering of biomaterials with GPCRs in therapeutical application." Authors Yuhong Jiang , Yuke Li , Xiujuan Fu , Yue Wu , Rujing Wang , Mengnan Zhao , Canquan Mao , Sanjun Shi Tags Drug delivery , Endosomal delivery , G protein-coupled receptors (GPCRs) , Molecular targeting , Nanoparticles , Signal transduction Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology Severity of neurological long-COVID symptoms correlates with increased level of autoantibodies targeting vasoregulatory and autonomic nervous system receptors Published date September 7, 2023 Abstract "Background: The Long-COVID syndrome constitutes a plethora of persisting symptoms with neurological disorders being the most disabling ones. The pathogenesis of Long-COVID is currently under heavy scrutiny and existing data on the role of auto-immune reaction to G-protein coupled receptors (GPCR) are conflicting. Methods: This monocentric, cross-sectional study included patients who suffered a mild to moderate SARS-CoV-2 infection up to 12 months prior to enrollment with (n = 72) or without (n = 58) Long-COVID diagnosis according to the German S1 guideline or with no known history of SARS-CoV-2 infection (n = 70). While autoantibodies towards the vasoregulation associated Adrenergic Receptor (ADR) B1 and B2 and the CNS and vasoregulation associated muscarinic acetylcholine receptor (CHR) M3 and M4 were measured by ELISA, neurological disorders were quantified by internationally standardized questionnaires. Results: The prevalence and concentrations of evaluated autoantibodes were significantly higher in Long-COVID compared to the 2 other groups (p = 2.1*10-9) with a significantly higher number of patients with simultaneous detection of more than one autoantibody in Long-COVID group (p = 0.0419). Importantly, the overall inflammatory state was low in all 3 groups. ARB1 and ARB2 correlated negatively CERAD Trail Marking A and B (R ≤ -0.26, p ≤ 0.043), while CHRM3 correlated positively with Chadler Fatigue Scale (R = 0.37, p = 0.0087). Conclusions: Concentrations of autoantibodies correlates to intensity of neurological disorders including psychomotor speed, visual search, attention, and fatigue." Authors Felix S Seibert , Ulrik Stervbo , Lea Wiemers , Sarah Skrzypczyk , Maximillian Hogeweg , Sebastian Bertram , Julia Kurek , Moritz Anft , Timm H Westhoff , Nina Babel Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology Pan-cancer functional analysis of somatic mutations in G protein-coupled receptors Published date December 1, 2022 Abstract G Protein-coupled receptors (GPCRs) are the most frequently exploited drug target family, moreover they are often found mutated in cancer. Here we used a dataset of mutations found in patient samples derived from the Genomic Data Commons and compared it to the natural human variance as exemplified by data from the 1000 genomes project. We explored cancer-related mutation patterns in all GPCR classes combined and individually. While the location of the mutations across the protein domains did not differ significantly in the two datasets, a mutation enrichment in cancer patients was observed among class-specific conserved motifs in GPCRs such as the Class A "DRY" motif. A Two-Entropy Analysis confirmed the correlation between residue conservation and cancer-related mutation frequency. We subsequently created a ranking of high scoring GPCRs, using a multi-objective approach (Pareto Front Ranking). Our approach was confirmed by re-discovery of established cancer targets such as the LPA and mGlu receptor families, but also discovered novel GPCRs which had not been linked to cancer before such as the P2Y Receptor 10 (P2RY10). Overall, this study presents a list of GPCRs that are amenable to experimental follow up to elucidate their role in cancer. Authors Bongers B J , Gorostiola González M , Wang X , van Vlijmen HWT , Jespers W , Gutiérrez-de-Terán H , Ye K , IJzerman AP , Heitman LH , van Westen GJP. Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology Chemokine Physiology in Cancer Published date November 1, 2022 Abstract Chemokines are chemotactic cytokines whose canonical functions govern movement of receptor expressing cells along chemical gradients. Chemokines are a physiologic system that is finely tuned by ligand and receptor expression, ligand or receptor oligomerization, redundancy, expression of atypical receptors and non-GPCR binding partners that cumulatively influence discrete pharmacological signaling responses and cellular functions. In cancer, chemokines play paradoxical roles in both the directed emigration of metastatic, receptor-expressing cancer cells out of the tumor as well as immigration of tumor infiltrating immune cells that culminate in a tumor unique immune microenvironment. In the age of precision oncology strategies to effectively harness the power of immunotherapy requires consideration of chemokine gradients within the unique spatial topography and temporal influences within heterogenous tumors. In this article we review current literature on the diversity of chemokine ligands and their cellular receptors that detect and process chemotactic gradients and illustrate how differences between ligand recognition and receptor activation influence the signaling machinery that drive cellular movement into and out of the tumor microenvironment. Facets of chemokine physiology across discrete cancer immune phenotypes are contrasted to existing chemokine-centered therapies in cancer. Authors Donovan Drouillard, Brian T Craig, Michael B Dwinell Tags Chemokine receptor; cell migration; immuno-oncology; metastasis; tumorigenesis. Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology The landscape of cancer-rewired GPCR signaling axes Published date May 8, 2024 Abstract "We explored the dysregulation of G-protein-coupled receptor (GPCR) ligand systems in cancer transcriptomics datasets to uncover new therapeutics opportunities in oncology. We derived an interaction network of receptors with ligands and their biosynthetic enzymes. Multiple GPCRs are differentially regulated together with their upstream partners across cancer subtypes and are associated to specific transcriptional programs and to patient survival patterns. The expression of both receptor-ligand (or enzymes) partners improved patient stratification, suggesting a synergistic role for the activation of GPCR networks in modulating cancer phenotypes. Remarkably, we identified many such axes across several cancer molecular subtypes, including many involving receptor-biosynthetic enzymes for neurotransmitters. We found that GPCRs from these actionable axes, including, e.g., muscarinic, adenosine, 5-hydroxytryptamine, and chemokine receptors, are the targets of multiple drugs displaying anti-growth effects in large-scale, cancer cell drug screens, which we further validated. We have made the results generated in this study freely available through a webapp (gpcrcanceraxes.bioinfolab.sns.it)." Authors Chakit Arora, Marin Matic, Luisa Bisceglia, Pierluigi Di Chiaro, Natalia De Oliveira Rosa, Francesco Carli, Lauren Clubb, Lorenzo Amir Nemati Fard, Giorgos Kargas, Giuseppe R Diaferia, Ranka Vukotic, Luana Licata, Guanming Wu, Gioacchino Natoli, J Silvio Gutkind , Francesco Raimondi Tags GPCR , cancer , cancer cell lines , cell-cell communication , drug repurposing , personalized medicine , signaling network , survival analysis , transcriptomics . Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology GPR56 signaling pathway network and its dynamics in the mesenchymal transition of glioblastoma Published date November 19, 2023 Abstract "G protein-coupled receptor 56 (GPR56/ADGRG1) is a multifunctional adhesion GPCR involved in diverse biological processes ranging from development to cancer. In our earlier study, we reported that GPR56 is expressed heterogeneously in glioblastoma (GBM) and is involved in the mesenchymal transition, making it a promising therapeutic target (Ganesh et al., 2022). Despite its important role in cancer, its mechanism of action or signaling is not completely understood. Thus, based on transcriptomic, proteomic, and phosphoproteomic differential expression data of GPR56 knockdown U373-GBM cells included in our above study along with detailed literature mining of the molecular events plausibly associated with GPR56 activity, we have constructed a signaling pathway map of GPR56 as may be applicable in mesenchymal transition in GBM. The map incorporates more than 100 molecular entities including kinases, receptors, ion channels, and others associated with Wnt, integrin, calcium signaling, growth factors, and inflammation signaling pathways. We also considered intracellular and extracellular factors that may influence the activity of the pathway entities. Here we present a curated signaling map of GPR56 in the context of GBM and discuss the relevance and plausible cross-connectivity across different axes attributable to GPR56 function. GPR56 signaling and mesenchymal transition." Authors Raksha A Ganesh , Krishnan Venkataraman , Ravi Sirdeshmukh Tags GPR56 /ADGRG1 , Mesenchymal transition , Pathway , Signaling , TG2 Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology GPR68-ATF4 signaling is a novel prosurvival pathway in glioblastoma activated by acidic extracellular microenvironment Published date January 31, 2024 Abstract " Background: Glioblastoma multiforme (GBM) stands as a formidable challenge in oncology because of its aggressive nature and severely limited treatment options. Despite decades of research, the survival rates for GBM remain effectively stagnant. A defining hallmark of GBM is a highly acidic tumor microenvironment, which is thought to activate pro-tumorigenic pathways. This acidification is the result of altered tumor metabolism favoring aerobic glycolysis, a phenomenon known as the Warburg effect. Low extracellular pH confers radioresistant tumors to glial cells. Notably GPR68, an acid sensing GPCR, is upregulated in radioresistant GBM. Usage of Lorazepam, which has off target agonism of GPR68, is linked to worse clinical outcomes for a variety of cancers. However, the role of tumor microenvironment acidification in GPR68 activation has not been assessed in cancer. Here we interrogate the role of GPR68 specifically in GBM cells using a novel highly specific small molecule inhibitor of GPR68 named Ogremorphin (OGM) to induce the iron mediated cell death pathway: ferroptosis. Method: OGM was identified in a non-biased zebrafish embryonic development screen and validated with Morpholino and CRISPR based approaches. Next, A GPI-anchored pH reporter, pHluorin2, was stably expressed in U87 glioblastoma cells to probe extracellular acidification. Cell survival assays, via nuclei counting and cell titer glo, were used to demonstrate sensitivity to GPR68 inhibition in twelve immortalized and PDX GBM lines. To determine GPR68 inhibition's mechanism of cell death we use DAVID pathway analysis of RNAseq. Our major indication, ferroptosis, was then confirmed by western blotting and qRT-PCR of reporter genes including TFRC. This finding was further validated by transmission electron microscopy and liperfluo staining to assess lipid peroxidation. Lastly, we use siRNA and CRISPRi to demonstrate the critical role of ATF4 suppression via GPR68 for GBM survival. Results: We used a pHLourin2 probe to demonstrate how glioblastoma cells acidify their microenvironment to activate the commonly over expressed acid sensing GPCR, GPR68. Using our small molecule inhibitor OGM and genetic means, we show that blocking GPR68 signaling results in robust cell death in all thirteen glioblastoma cell lines tested, irrespective of genetic and phenotypic heterogeneity, or resistance to the mainstay GBM chemotherapeutic temozolomide. We use U87 and U138 glioblastoma cell lines to show how selective induction of ferroptosis occurs in an ATF4-dependent manner. Importantly, OGM was not-acutely toxic to zebrafish and its inhibitory effects were found to spare non-malignant neural cells. Conclusion: These results indicate GPR68 emerges as a critical sensor for an autocrine pro-tumorigenic signaling cascade triggered by extracellular acidification in glioblastoma cells. In this context, GPR68 suppresses ATF4, inhibition of GPR68 increases expression of ATF4 which leads to ferroptotic cell death. These findings provide a promising therapeutic approach to selectively induce ferroptosis in glioblastoma cells while sparing healthy neural tissue." Authors Charles H Williams , Leif R Neitzel , Jessica Cornell , Samantha Rea , Ian Mills , Maya S Silver , Jovanni D Ahmad , Konstantin G Birukov , Anna Birukova , Henry Brem , Betty Tyler , Eli E Bar , Charles C Hong Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

Dr. GPCR Podcast << Back to podcast list Dr. Debbie Hay About this episode Dr. Debbie Hay is presently a professor at the Department of Pharmacology and Toxicology at the University of Otago after spending 18 years at the University of Auckland. Her work is primarily focused on class B GPCRs and their interactions with RAMPs. Debbie obtained a Ph.D. in Molecular Pharmacology from Imperial College London in the UK. She has gained experience from working in academia and at GSK as an industrial trainee. Join me and learn more about Debbie’s career and what she learned through her experiences as a scientist. Dr. Debbie Hay on the web LinkedIn Wikipedia University of Otago University of Auckland Google Scholar Pubmed Research Gate Twitter Dr. GPCR Ecosystem Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

< GPCR News < GPCRs in Oncology and Immunology GPR4 in the pH-dependent migration of melanoma cells in the tumor microenvironment Published date December 23, 2022 Abstract Due to its high metastatic potential, malignant melanoma is one of the deadliest skin cancers. In melanoma as well as in other cancers, acidification of the tumor microenvironment (= TME, inverse pH-gradient) is a well-known driver of tumor progression and metastasis. Membrane-bound receptors, such as the proton-sensitive GPCR (pH-GPCR) GPR4, are considered as potential initiators of the signaling cascades relevant to malignant transformation. In this study, we investigated the pH-dependent migration of GPR4 wildtype/overexpressing SK-Mel-28 cells by using an impedance-based electrical wounding and migration assay and classical Boyden chamber experiments. Migration of GPR4 overexpressing SK-Mel-28 cells was enhanced in a range of pH 6.5 - pH 7.5 as compared to controls in the impedance-based electrical wounding and migration assay. In Boyden chamber experiments, GPR4 overexpression only increased migration at pH 7.5 in a Matrigel-free setup, but not at pH 6.5. Results indicate that GPR4 is involved in the migration of melanoma cells, especially in the tumor periphery, and that this process is affected by pH in the TME. Authors Judith Anthea Stolwijk , Susanne Wallner , Judith Heider , Bernadett Kurz , Lisa Pütz , Stefanie Michaelis , Barbara Goricnik , Julia Erl , Linda Frank , Mark Berneburg , Frank Haubner , Joachim Wegener , Stephan Schreml Tags Boyden chamber , ECIS , GPR4 , impedance , malignant melanoma , migration , pH-GPCR. Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

Dr. GPCR Podcast << Back to podcast list Dr. Khaled Abdelrahman About Dr. Khaled Abdelrahman Dr. Khaled Abdelrahman graduated in 2006 with a BSc in Pharmaceutical Sciences from Alexandria University (Egypt) followed by MSc in Pharmacology in the same university that was conferred in 2009. He joined the laboratory of Dr. William Cole at the University of Calgary in 2010 for his Ph.D. where he studied the molecular basis underlying altered cerebrovascular function and blood flow in type 2 diabetes. In 2015, He joined Dr. Stephen Ferguson’s laboratory in the Departments of Cellular & Molecular Medicine and Neuroscience at the University of Ottawa as a Postdoctoral Fellow to explore novel G protein-coupled receptor (GPCR) candidates that can be targeted pharmacologically to slow neurodegeneration. He has been also studying what aspects of GPCR signaling are regulated in a sex-selective manner and how this can influence drug discovery in the area of neurodegenerative diseases. He is also a Registered Pharmacist in Canada and held two of the most prestigious Clinician Postdoctoral Fellowships offered by Alberta Innovates and Canadian Institutes of Health Research. He received the Canadian Society of Pharmacology and Therapeutics Postdoctoral and Publication awards along with many Young Scientist Awards from the American Society for Pharmacology and Experimental Therapeutics. Dr. Khaled Abdelrahman on the web Twitter PubMed Google Scholar Dr. GPCR Ecosystem Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

Dr. GPCR Podcast << Back to podcast list Dr. Silvia Sposini About Dr. Silvia Sposini " I'm originally from Rome, Italy, where I studied Biological Sciences as a BSc student. I moved to London as a short experience (3 months) during my MSc but I ended up staying for a full year and and a PhD! During my time in London I investigated regulatory mechanisms of GPCR action, namely dimerization and membrane trafficking, in Dr Aylin Hanyaloglu 's lab at Imperial College London. In 2018 I got married and moved to France, to join the Interdisciplinary Institute for Neurosciences in Bordeaux. Still working on GPCR trafficking but this time in neurons. In 2021 I became mum of a gorgeous baby girl, Elena. I am currently funded by a postdoctoral fellowship from Wellcome Trust, working on a collaborative project (Dr Hanyaloglu's lab at ICL + Dr Perrais' lab at IINS) focused on understanding the interplay between GPCR signalling and trafficking in neurons using microscopy and proteomics based techniques. " Dr. Silvia Sposini on the web Bordeaux Neurocampus LinkedIn ResearchGate X (Twitter) Dr. GPCR Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

Dr. GPCR Podcast << Back to podcast list Dr. Gregory Tall About Dr. Gregory Tall " Dr. Gregory Tall earned his Ph.D. in Biomedical Sciences from U.T. Southwestern Medical Center with Bruce Horazdovsky, Ph.D. They worked on the interactome of yeast and mammalian Rab5 homologs including identification of Rab5 GEFs. In 2000, Dr. Tall moved upstairs to conduct his postdoctoral work on heterotrimeric G proteins and the novel interactor, Ric-8 with Alfred Gilman, M.D. Ph.D. In 2007, Dr. Tall joined the faculty in the Department of Pharmacology and Physiology at the University of Rochester Medical Center, there establishing his lab and major research directions. Dr. Tall moved to the University of Michigan in 2016 as an Associate Professor of Pharmacology and is a current active member of the department. The current goals of the Tall lab are to understand the basic mechanism by which Ric-8 proteins fold all heterotrimeric G protein alpha subunits, to exploit a Ric-8-based technology to purify recombinant G proteins and to use the G proteins in assays to explore the mechanisms of action of the 33-member adhesion GPCR family or Family B2 GPCRs. We found that adhesion GPCRs are activated by a tethered peptide agonist mechanism that differed from the common example known at the time, protease activated receptors (PARs). PARs have an N-terminal leader sequence that is clipped by exogenous proteases to reveal a new N-terminus that serves as the tethered agonist. Adhesion GPCRs pre-cleave themselves and the two resultant fragments of the receptor remain together to conceal the tethered peptide agonist. Mechanical dissociation of the two fragments aided by protein binding ligands and cell movement serves to decrypt the tethered agonist for binding to its orthosteric site. Our current goals are to explore this mechanism in detail and to understand how it may happen for the 33 adhesion GPCRs in complex physiological contexts…one being our discovery that GPR56 is the platelet receptor that senses collagen and shear force to initiate the platelet activation program. Dr. Tall has been continuously funded by the NIH since receiving an early RO1 award at Rochester. He has continued funding at Michigan through the MIRA R35 program. Dr. Tall has presented his work at 59 invited seminars including national and international meetings and academic departmental seminars. " Dr. Gregory Tall on the web The Tall Lab University of Michigan Google Scholar Twitter Dr. GPCR Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>