ArticleBiochemistry2006
Mutations of CB1 T210 produce active and inactive receptor forms: correlations with ligand affinity, receptor stability, and cellular localization.
Article in Biochemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
- Article
- Molecular mechanism of allosteric modulation for the cannabinoid receptor CB1.Nature chemical biology · 2022Article
- CB1 Cannabinoid Receptor Signaling and Biased Signaling.Molecules (Basel, Switzerland) · 2021Review
- In Vitro and In Silico Characterization of G-Protein Coupled Receptor (GPCR) Targets of Phlorofucofuroeckol-A and Dieckol.Marine drugs · 2021Article
- A novel bioassay for quantification of surface Cannabinoid receptor 1 expression.Scientific reports · 2020Article
- Article
- Probing thermostability of detergent-solubilized CBThe Journal of biological chemistry · 2020Article
- Allosteric modulators restore orthosteric agonist binding to mutated CBThe Journal of pharmacy and pharmacology · 2020Article
- Protein Interactors and Trafficking Pathways That Regulate the Cannabinoid Type 1 Receptor (CB1R).Frontiers in molecular neuroscience · 2020Review
- Structural Insights into CB1 Receptor Biased Signaling.International journal of molecular sciences · 2019Review
- Pyrimidinyl Biphenylureas Act as Allosteric Modulators to Activate Cannabinoid Receptor 1 and InitiateMolecular pharmacology · 2019Article
- The F238L Point Mutation in the Cannabinoid Type 1 Receptor Enhances Basal Endocytosis via Lipid Rafts.Frontiers in molecular neuroscience · 2018Article
- Modulation of CB1 cannabinoid receptor by allosteric ligands: Pharmacology and therapeutic opportunities.Neuropharmacology · 2017Review
- Article
- The G protein GThe Journal of biological chemistry · 2017Article
- Assessing Allosteric Modulation of CBMethods in enzymology · 2017Article
- Article
- Article
- Computational Prediction and Biochemical Analyses of New Inverse Agonists for the CB1 Receptor.Journal of chemical information and modeling · 2016Article
- Multiple Forms of Endocannabinoid and Endovanilloid Signaling Regulate the Tonic Control of GABA Release.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Human cannabinoid receptor 1 (CB(1)) has attracted substantial interest as a potential therapeutic target for treating obesity and other obsessive disorders. An understanding of the mechanism governing the transition of the CB(1) receptor between its inactive and active states is critical for understanding how therapeutics can selectively regulate receptor activity. We have examined the importance of the Thr at position 210 in CB(1) in this transition, a residue predicted to be on the same face of the helix as the Arg of the DRY motif highly conserved in the G protein-coupled receptor superfamily. This Thr was substituted with Ile and Ala via mutagenesis, and the receptors, T210I and T210A, were expressed in HEK 293 cells. The T210I receptor exhibited enhanced agonist and diminished inverse agonist affinity relative to the wild type, consistent with a shift toward the active form. However, treatment with GTPgammaS to inhibit G protein coupling diminished the affinity change for the inverse agonist SR141716A. The decreased thermal stability of the T210I receptor and increased level of internalization of a T210I receptor-GFP chimera were also observed, consistent with constitutive activity. In contrast, the T210A receptor exhibited the opposite profile: diminished agonist and enhanced inverse agonist affinity. The T210A receptor was found to be more thermally stable than the wild type, and high levels of a T210A receptor-GFP chimera were localized to the cell surface as predicted for an inactive receptor form. These results suggest that T210 plays a key role in governing the transition between inactive and active CB(1) receptor states.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.