ArticleBritish journal of pharmacology2013
Novel roles for β-arrestins in the regulation of pharmacological sequestration to predict agonist-induced desensitization of dopamine D3 receptors.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 51 citations in OpenAlex.
- Mdm2-Mediated Ubiquitination Plays a Pivotal Role in Differentiating the Endocytic Roles of GRK2 and Arrestin3.International journal of molecular sciences · 2025Article
- Transactivation of the EGF receptor as a novel desensitization mechanism for G protein-coupled receptors, illustrated by dopamine D2-like and βCellular & molecular biology letters · 2024Article
- Biased Signaling Agonists Promote Distinct Phosphorylation and Conformational States of the Dopamine D3 Receptor.International journal of molecular sciences · 2024Article
- The Ubiquitination of Arrestin3 within the Nucleus Triggers the Nuclear Export of Mdm2, Which, in Turn, Mediates the Ubiquitination of GRK2 in the Cytosol.International journal of molecular sciences · 2024Article
- Substance Addiction Rehabilitation Drugs.Pharmaceuticals (Basel, Switzerland) · 2024Review
- TRAF6-mediated ubiquitination of AKT in the nucleus is a critical event underlying the desensitization of G protein-coupled receptors.Cell communication and signaling : CCS · 2024Article
- Unveiling the Differences in Signaling and Regulatory Mechanisms between Dopamine DInternational journal of molecular sciences · 2023Review
- Dopamine Receptor DThe Yale journal of biology and medicine · 2023Review
- Sequestration of Gβγ by deubiquitinated arrestins into the nucleus as a novel desensitization mechanism of G protein-coupled receptors.Cell communication and signaling : CCS · 2023Article
- Dopamine D3 Receptor in Parkinson Disease: A Prognosis Biomarker and an Intervention Target.Current topics in behavioral neurosciences · 2023Article
- Mechanistic diversity involved in the desensitization of G protein-coupled receptors.Archives of pharmacal research · 2021Review
- Neuronal Dopamine D3 Receptors: Translational Implications for Preclinical Research and CNS Disorders.Biomolecules · 2021Review
- Review
- A Split Luciferase Complementation Assay for the Quantification of β-Arrestin2 Recruitment to Dopamine DInternational journal of molecular sciences · 2020Article
- DRD3 (dopamine receptor D3) but not DRD2 activates autophagy through MTORC1 inhibition preserving protein synthesis.Autophagy · 2020Article
- Role of Helix 8 in Dopamine Receptor Signaling.Biomolecules & therapeutics · 2019Article
- Molecular Signature That Determines the Acute Tolerance of G Protein-Coupled Receptors.Biomolecules & therapeutics · 2017Article
- Functional Characterization of a Novel Series of Biased Signaling Dopamine D3 Receptor Agonists.ACS chemical neuroscience · 2017Article
- Multifactorial Regulation of G Protein-Coupled Receptor Endocytosis.Biomolecules & therapeutics · 2017Review
- Functional Regulation of Dopamine D₃ Receptor through Interaction with PICK1.Biomolecules & therapeutics · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeIn addition to typical GPCR kinase (GRK)-/β-arrestin-dependent internalization, dopamine D3 receptor employed an additional GRK-independent sequestration pathway. In this study, we investigated the molecular mechanism of this novel sequestration pathway. EXPERIMENTAL APPROACH: Radioligand binding, flow cytometry and cell surface biotinylation assay were used to characterize trafficking properties of D2 and D3 receptors. Serine/threonine and N-linked glycosylation mutants of the D3 receptor were utilized to locate receptor regions involved in pharmacological sequestration and desensitization. Various point mutants of the D2 and D3 receptors, whose sequestration and desensitization properties were altered, were combined with knockdown cells of GRKs or β-arrestins to functionally correlate pharmacological sequestration and desensitization. KEY
resultsThe D3 receptor, but not the D2 receptor, showed characteristic trafficking behaviour in which receptors were shifted towards the more hydrophobic domains within the plasma membrane without translocation into other intracellular compartments. Among various amino acid residues tested, S145/S146, C147 and N12/19 were involved in pharmacological sequestration and receptor desensitization. Both pharmacological sequestration and desensitization of D3 receptor required β-arrestins, and functional relationship was observed between two processes when it was tested for D3 receptor variants and agonists. CONCLUSIONS AND IMPLICATIONS: Pharmacological sequestration of D3 receptor accompanies movement of cell surface receptors into a more hydrophobic fraction within the plasma membrane and renders D3 receptor inaccessible to hydrophilic ligands. Pharmacological sequestration is correlated with desensitization of the D3 receptor in a Gβγ- and β-arrestin-dependent manner. This study provides new insights into molecular mechanism governing GPCR trafficking and desensitization.
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