ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Identification of two functionally distinct endosomal recycling pathways for dopamine D₂ receptor.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Rab4 spatially and functionally converges with Rab7 in the degradative endolysosomal network.Molecular biology of the cell · 2026Article
- Association of the endosomal sorting processes cargo selection and membrane tubulation with human reward system reactivity.European archives of psychiatry and clinical neuroscience · 2026Article
- Synaptojanin-1 supports VPS35-dependent trafficking of dopamine D2 autoreceptors at presynaptic terminals.Research square · 2025Article
- Cholesterol-activated stress granules reduce the membrane localization of DRD2 and promote prolactinoma dopamine agonists resistance.Acta neuropathologica communications · 2025Article
- Synaptotagmin-11 deficiency mediates schizophrenia-like behaviors in mice via dopamine over-transmission.Nature communications · 2024Article
- Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia: randomized trials and multiomics analysis.Military Medical Research · 2023Article
- Sleep Deprivation Induces Dopamine System Maladaptation and Escalated Corticotrophin-Releasing Factor Signaling in Adolescent Mice.Molecular neurobiology · 2023Article
- Proton-gated coincidence detection is a common feature of GPCR signaling.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Tumor suppressor DRD2 facilitates M1 macrophages and restricts NF-κB signaling to trigger pyroptosis in breast cancer.Theranostics · 2021Article
- Trappc9 deficiency in mice impairs learning and memory by causing imbalance of dopamine D1 and D2 neurons.Science advances · 2020Article
- A biohybrid synapse with neurotransmitter-mediated plasticity.Nature materials · 2020Article
- RGS9-2 rescues dopamine D2 receptor levels and signaling inEMBO molecular medicine · 2019Article
- Effects of social defeat stress on dopamine D2 receptor isoforms and proteins involved in intracellular trafficking.Behavioral and brain functions : BBF · 2018Article
- Interplay between adenosine receptor antagonist and cyclooxygenase inhibitor in haloperidol-induced extrapyramidal effects in mice.Metabolic brain disease · 2018Article
- Structure-Activity Investigation of a G Protein-Biased Agonist Reveals Molecular Determinants for Biased Signaling of the DFrontiers in synaptic neuroscience · 2018Article
- Whole-transcriptome microarray analysis reveals regulation of Rab4 by RBM5 in neurons.Neuroscience · 2017Article
- BDNF rescues prefrontal dysfunction elicited by pyramidal neuron-specific DTNBP1 deletion in vivo.Journal of molecular cell biology · 2017Article
- Imaging GPCRs trafficking and signaling with total internal reflection fluorescence microscopy in cultured neurons.Methods in cell biology · 2016Article
- Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain.Translational psychiatry · 2015Article
- Imaging the Insertion of Superecliptic pHluorin-Labeled Dopamine D2 Receptor Using Total Internal Reflection Fluorescence Microscopy.Current protocols in neuroscience · 2015Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dopamine D₂ receptor (DRD2) is important for normal function of the brain reward circuit. Lower DRD2 function in the brain increases the risk for substance abuse, obesity, attention deficit/hyperactivity disorder, and depression. Moreover, DRD2 is the target of most antipsychotics currently in use. It is well known that dopamine-induced DRD2 endocytosis is important for its desensitization. However, it remains controversial whether DRD2 is recycled back to the plasma membrane or targeted for degradation following dopamine stimulation. Here, we used total internal reflection fluorescent microscopy (TIRFM) to image DRD2 with a superecliptic pHluorin tagged to its N terminus. With these technical advances, we were able to directly visualize vesicular insertion events of DRD2 in cultured mouse striatal medium spiny neurons. We showed that insertion of DRD2 occurs on neuronal somatic and dendritic surfaces. Lateral diffusion of DRD2 was observed following its insertion. Most importantly, using our new approach, we uncovered two functionally distinct recycling pathways for DRD2: a constitutive recycling pathway and a dopamine activity-dependent recycling pathway. We further demonstrated that Rab4 plays an important role in constitutive DRD2 recycling, while Rab11 is required for dopamine activity-dependent DRD2 recycling. Finally, we demonstrated that the two DRD2 recycling pathways play distinct roles in determining DRD2 function: the Rab4-sensitive constitutive DRD2 recycling pathway determines steady-state surface expression levels of DRD2, whereas the Rab11-sensitive dopamine activity-dependent DRD2 recycling pathway is important for functional resensitization of DRD2. Our findings underscore the significance of endosomal recycling in regulation of DRD2 function.
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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.