ArticleThe Journal of biological chemistry2016
The Orphan G Protein-coupled Receptor GPR17 Negatively Regulates Oligodendrocyte Differentiation via Gαi/o and Its Downstream Effector Molecules.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 77 citations in OpenAlex.
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- Oxysterol signaling in the central nervous system: cellular mechanisms and implications for neurodegeneration.Frontiers in molecular neuroscience · 2026Review
- Selective GPR17 antagonism enhances structural and functional recovery in animal models of demyelination.PloS one · 2026Article
- Review
- High-rate mechano-stimulation alters proliferation- and maturation-related signaling of oligodendrocyte precursor cells in a 3D hydrogel.Mechanobiology in medicine · 2025Article
- Inhibition of GPR17/ID2 Axis Improve Remyelination and Cognitive Recovery after SAH by Mediating OPC Differentiation in Rat Model.Translational stroke research · 2025Article
- The aminosteroid U73122 promotes oligodendrocytes generation and myelin formation.Acta pharmacologica Sinica · 2024Article
- Impact of the Voltage-Gated Calcium Channel Antagonist Nimodipine on the Development of Oligodendrocyte Precursor Cells.International journal of molecular sciences · 2023Article
- Cryo-EM structure of G-protein-coupled receptor GPR17 in complex with inhibitory G protein.MedComm · 2022Article
- Article
- A Glance at the Molecules That Regulate Oligodendrocyte Myelination.Current issues in molecular biology · 2022Review
- Antibody cross-reactivity between casein and myelin-associated glycoprotein results in central nervous system demyelination.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A review of non-prostanoid, eicosanoid receptors: expression, characterization, regulation, and mechanism of action.Journal of cell communication and signaling · 2022Review
- Intestinal Gpr17 deficiency improves glucose metabolism by promoting GLP-1 secretion.Cell reports · 2022Article
- The oligodendrocyte-enriched orphan G protein-coupled receptor Gpr62 is dispensable for central nervous system myelination.Neural development · 2021Article
- Involvement of GPR17 in Neuronal Fibre Outgrowth.International journal of molecular sciences · 2021Article
- Synthesis and Preclinical Validation of Novel Indole Derivatives as a GPR17 Agonist for Glioblastoma Treatment.Journal of medicinal chemistry · 2021Article
- Keeping the ageing brain wired: a role for purine signalling in regulating cellular metabolism in oligodendrocyte progenitors.Pflugers Archiv : European journal of physiology · 2021Review
- The white matter is a pro-differentiative niche for glioblastoma.Nature communications · 2021Article
- Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies have recognized G protein-coupled receptors as important regulators of oligodendrocyte development. GPR17, in particular, is an orphan G protein-coupled receptor that has been identified as oligodendroglial maturation inhibitor because its stimulation arrests primary mouse oligodendrocytes at a less differentiated stage. However, the intracellular signaling effectors transducing its activation remain poorly understood. Here, we use Oli-neu cells, an immortalized cell line derived from primary murine oligodendrocytes, and primary rat oligodendrocyte cultures as model systems to identify molecular targets that link cell surface GPR17 to oligodendrocyte maturation blockade. We demonstrate that stimulation of GPR17 by the small molecule agonist MDL29,951 (2-carboxy-4,6-dichloro-1H-indole-3-propionic acid) decreases myelin basic protein expression levels mainly by triggering the Gαi/o signaling pathway, which in turn leads to reduced activity of the downstream cascade adenylyl cyclase-cAMP-PKA-cAMP response element-binding protein (CREB). In addition, we show that GPR17 activation also diminishes myelin basic protein abundance by lessening stimulation of the exchange protein directly activated by cAMP (EPAC), thus uncovering a previously unrecognized role for EPAC to regulate oligodendrocyte differentiation. Together, our data establish PKA and EPAC as key downstream effectors of GPR17 that inhibit oligodendrocyte maturation. We envisage that treatments augmenting PKA and/or EPAC activity represent a beneficial approach for therapeutic enhancement of remyelination in those demyelinating diseases where GPR17 is highly expressed, such as multiple sclerosis.
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