ArticleBritish journal of pharmacology2014
Heteromerization of GPR55 and cannabinoid CB2 receptors modulates signalling.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 126 citations in OpenAlex.
- Astrocytic GPR55 receptors promote glycolysis.Journal of cannabis research · 2026Article
- Cannabinoid type 2 receptor crosstalk and microglial plasticity-shaping the balance between neuroinflammation and repair.Inflammopharmacology · 2026Review
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- Emerging roles of cannabinoid pathways in renal injury and repair.Frontiers in pharmacology · 2026Review
- Synthesis of Novel Chloro-Benzo [Pharmaceuticals (Basel, Switzerland) · 2025Article
- Benzo[International journal of molecular sciences · 2025Article
- Two-Step Cell Death Induction by the New 2-Arachidonoyl Glycerol Analog and Its Modulation by Lysophosphatidylinositol in Human Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Cannabinoids: Role in Neurological Diseases and Psychiatric Disorders.International journal of molecular sciences · 2024Review
- From Classical to Alternative Pathways of 2-Arachidonoylglycerol Synthesis: AlterAGs at the Crossroad of Endocannabinoid and Lysophospholipid Signaling.Molecules (Basel, Switzerland) · 2024Review
- Article
- Heteromers Formed by GPR55 and Either Cannabinoid CBInternational journal of molecular sciences · 2024Article
- The Interaction of the Endocannabinoid Anandamide and Paracannabinoid Lysophosphatidylinositol during Cell Death Induction in Human Breast Cancer Cells.International journal of molecular sciences · 2024Article
- Article
- Exploring orphan GPCRs in neurodegenerative diseases.Frontiers in pharmacology · 2024Review
- Article
- Lysophosphatidylinositol Promotes Chemotaxis and Cytokine Synthesis in Mast Cells with Differential Participation of GPR55 and CB2 Receptors.International journal of molecular sciences · 2023Article
- The Mechanisms of GPR55 Receptor Functional Selectivity during Apoptosis and Proliferation Regulation in Cancer Cells.International journal of molecular sciences · 2023Article
- Identification of a novel fatty acid binding protein-5-CB2 receptor-dependent mechanism regulating anxiety behaviors in the prefrontal cortex.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Identification of Novel CB2 Ligands through Virtual Screening and In Vitro Evaluation.Journal of chemical information and modeling · 2023Article
- Endocannabinoid-Binding Receptors as Drug Targets.Methods in molecular biology (Clifton, N.J.) · 2023Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeHeteromerization of GPCRs is key to the integration of extracellular signals and the subsequent cell response via several mechanisms including heteromer-selective ligand binding, trafficking and/or downstream signalling. As the lysophosphatidylinositol GPCR 55 (GPR55) has been shown to affect the function of the cannabinoid receptor subtype 2 (CB2 receptor) in human neutrophils, we investigated the possible heteromerization of CB2 receptors with GPR55. EXPERIMENTAL APPROACH: The direct interaction of human GPR55 and CB2 receptors heterologously expressed in HEK293 cells was assessed by co-immunoprecipitation and bioluminescence resonance energy transfer assays. The effect of cross-talk on signalling was investigated at downstream levels by label-free real-time methods (Epic dynamic mass redistribution and CellKey impedance assays), ERK1/2-MAPK activation and gene reporter assays. KEY
resultsGPR55 and CB2 receptors co-localized on the surface of HEK293 cells, co-precipitated in membrane extracts and formed heteromers in living HEK293 cells. Whereas heteromerization led to a reduction in GPR55-mediated activation of transcription factors (nuclear factor of activated T-cells, NF-κB and cAMP response element), ERK1/2-MAPK activation was potentiated in the presence of CB2 receptors. CB2 receptor-mediated signalling was also affected by co-expression with GPR55. Label-free assays confirmed cross-talk between the two receptors. CONCLUSIONS AND IMPLICATIONS: Heteromers, unique signalling units, form in HEK293 cells expressing GPR55 and CB2 receptors. The signalling by agonists of either receptor was governed (i) by the presence or absence of the partner receptors (with the consequent formation of heteromers) and (ii) by the activation state of the partner receptor.
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