ArticleJournal of neurochemistry2018
The orphan G-protein-coupled receptor 75 signaling is activated by the chemokine CCL5.
Article in Journal of neurochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Hepatic GPR75 exacerbates MASH through GNAI2-dependent signaling.Hepatology (Baltimore, Md.) · 2026Article
- G protein-coupled receptor 75 mediates depression-like behaviors and HPA axis hyperactivity through an excitatory arcuate-paraventricular nucleus circuit.Acta pharmacologica Sinica · 2026Article
- International Union of Basic and Clinical Pharmacology. CXXII. Applying an objective evaluation to the status of class A orphan G protein-coupled receptors.Pharmacological reviews · 2026Review
- GPR75 in glutamatergic neurons regulates body weight.Cell reports · 2026Article
- Gpr75 Deletion in Adipocytes Protects From Diet-Induced Obesity: Changes in Glucose Homeostasis and Inflammatory Responses.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Anatomical and Neuronal Distribution of the G-Coupled Protein Receptor 75 mRNA in the Mouse Central Nervous System.The European journal of neuroscience · 2026Article
- Neuronal GPR75 deficiency protects against diet-induced obesity in a humanized mouse model.Science advances · 2026Article
- CCL5 paradoxically regulates glomerular injury by skewing macrophage polarization.JCI insight · 2025Article
- Human immunodeficiency virus 1 glycoprotein 120 induces endoplasmic reticulum stress in neurons.Cell death & disease · 2025Article
- GPR75: Advances, Challenges in Deorphanization, and Potential as a Novel Drug Target for Disease Treatment.International journal of molecular sciences · 2025Review
- Ciliary localization of GPR75 promotes fat accumulation in mice.The Journal of clinical investigation · 2024Article
- Central regulation of feeding and body weight by ciliary GPR75.The Journal of clinical investigation · 2024Article
- Review
- Global and endothelial G-protein coupled receptor 75 (GPR75) knockout relaxes pulmonary artery and mitigates hypoxia-induced pulmonary hypertension.Vascular pharmacology · 2023Article
- Gpr75 knockout mice display age-dependent cone photoreceptor cell loss.Journal of neurochemistry · 2023Article
- CCL5 might be a prognostic biomarker and associated with immuno-therapeutic efficacy in cancers: A pan-cancer analysis.Heliyon · 2023Article
- Mice deficient for G-protein-coupled receptor 75 display altered presynaptic structural protein expression and disrupted fear conditioning recall.Journal of neurochemistry · 2023Article
- G Protein-Coupled Receptor 75 (GPR75) As a Novel Molecule for Targeted Therapy of Cancer and Metabolic Syndrome.Asian Pacific journal of cancer prevention : APJCP · 2023Review
- Gpr75-deficient mice are protected from high-fat diet-induced obesity.Obesity (Silver Spring, Md.) · 2023Article
- Article
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Authors and funding
5 authors.
Funding
Abstract
The chemokine CCL5 prevents neuronal cell death mediated both by amyloid β, as well as the human immunodeficiency virus viral proteins gp120 and Tat. Because CCL5 binds to CCR5, CCR3 and/or CCR1 receptors, it remains unclear which of these receptors plays a role in neuroprotection. Indeed, CCL5 also has neuroprotective activity in cells lacking these receptors. CCL5 may bind to a G-protein-coupled receptor 75 (GPR75), which encodes for a 540 amino-acid orphan receptor of the Gqα family. In this study, we have used SH-SY5Y human neuroblastoma cells to characterize whether CCL5 could activate a Gq signaling through GPR75. Both qPCR and flow cytometry show that these cells express GPR75 but do not express CCR5, CCR3 or CCR1 receptors. SY-SY5Y cells were then used to examine CCL5-mediated signaling. We report that CCL5 promotes a time- and concentration-dependent phosphorylation of protein kinase B (AKT), glycogen synthase kinase 3β, and extracellular signal-regulated kinase (ERK) 1/2. Specific antagonists of CCR5, CCR3, and CCR1 did not prevent CCL5 from increasing phosphorylated AKT or ERK. Moreover, CCL5 promotes a time-dependent internalization of GPR75. Lastly, knocking down GPR75 expression by a CRISPR-Cas9 approach inhibited the ability of CCL5 to activate pERK in SH-SY5Y cells. Therefore, we propose that GPR75 is a novel receptor for CCL5 that could explain some of the pharmacological action of this chemokine. These findings may help in the development of small molecule GPR75 agonists that mimic CCL5. Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/.
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