ArticleBritish journal of pharmacology2012
The N-terminal region of the dopamine D2 receptor, a rhodopsin-like GPCR, regulates correct integration into the plasma membrane and endocytic routes.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Constitutive and Conditional Epitope Tagging of Endogenous G-Protein-Coupled Receptors inThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Pathogenic Impact of Fatty Acid-Binding Proteins in Parkinson's Disease-Potential Biomarkers and Therapeutic Targets.International journal of molecular sciences · 2023Review
- Unveiling the Differences in Signaling and Regulatory Mechanisms between Dopamine DInternational journal of molecular sciences · 2023Review
- Amelioration of Nicotine-Induced Conditioned Place Preference Behaviors in Mice by an FABP3 Inhibitor.International journal of molecular sciences · 2023Article
- The dopaminergic control of Cushing's syndrome.Journal of endocrinological investigation · 2022Review
- Cholesterol-dependent endocytosis of GPCRs: implications in pathophysiology and therapeutics.Biophysical reviews · 2021Review
- Impact of Fatty Acid-Binding Proteins in α-Synuclein-Induced Mitochondrial Injury in Synucleinopathy.Biomedicines · 2021Review
- Dopamine D2 Long Receptors Are Critical for Caveolae-Mediated α-Synuclein Uptake in Cultured Dopaminergic Neurons.Biomedicines · 2021Article
- Review
- Glycosylation and raft endocytosis in cancer.Cancer metastasis reviews · 2020Review
- N-glycosylation of αScientific reports · 2020Article
- RGS9-2 rescues dopamine D2 receptor levels and signaling inEMBO molecular medicine · 2019Article
- βScientific reports · 2017Article
- Ligand binding pocket of a novel Allatostatin receptor type C of stick insect, Carausius morosus.Scientific reports · 2017Article
- Dopamine-2 receptor extracellular N-terminus regulates receptor surface availability and is the target of human pathogenic antibodies from children with movement and psychiatric disorders.Acta neuropathologica communications · 2016Article
- The N-terminus of the yeast G protein-coupled receptor Ste2p plays critical roles in surface expression, signaling, and negative regulation.Biochimica et biophysica acta · 2016Article
- Lys39-Lysophosphatidate Carbonyl Oxygen Interaction Locks LPA1 N-terminal Cap to the Orthosteric Site and partners Arg124 During Receptor Activation.Scientific reports · 2015Article
- Single and binge methamphetamine administrations have different effects on the levels of dopamine D2 autoreceptor and dopamine transporter in rat striatum.International journal of molecular sciences · 2014Article
- Serum IgE clearance is facilitated by human FcεRI internalization.The Journal of clinical investigation · 2014Article
- High-throughput flow cytometry cell-based assay to detect antibodies to N-methyl-D-aspartate receptor or dopamine-2 receptor in human serum.Journal of visualized experiments : JoVE · 2013Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeFunctional roles of the N-terminal region of rhodopsin-like GPCR family remain unclear. Using dopamine D(2) and D(3) receptors as a model system, we probed the roles of the N-terminal region in the signalling, intracellular trafficking of receptor proteins, and explored the critical factors that determine the functionality of the N-terminal region. EXPERIMENTAL APPROACH: The N-terminal region of the D(2) receptor was gradually shortened or switched with that of the D(3) receptor or a non-specific sequence (FLAG), or potential N-terminal glycosylation sites were mutated. Effects of these manipulations on surface expression, internalization, post-endocytic behaviours and signalling were determined. KEY
resultsShortening the N-terminal region of the D(2) receptor enhanced receptor internalization and impaired surface expression and signalling; ligand binding, desensitization and down-regulation were not affected but their association with a particular microdomain, caveolae, was disrupted. Replacement of critical residues within the N-terminal region with the FLAG epitope failed to restore surface expression but partially restored the altered internalization and signalling. When the N-terminal regions were switched between D(2) and D(3) receptors, cell surface expression pattern of each receptor was switched. Mutations of potential N-terminal glycosylation sites inhibited surface expression but enhanced internalization of D(2) receptors. CONCLUSIONS AND IMPLICATIONS: Shortening of N-terminus or mutation of glycosylation sites located within the N-terminus enhanced receptor internalization but impaired the surface expression of D(2) receptors. The N-terminal region of the D(2) receptor, in a sequence-specific manner, controls the receptor's conformation and integration into the plasma membrane, which determine its subcellular localization, intracellular trafficking and signalling properties.
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