ArticleThe Journal of biological chemistry2010
A biochemical and functional protein complex involving dopamine synthesis and transport into synaptic vesicles.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 140 citations in OpenAlex.
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- Lactoperoxidase is a candidate for mediating neuromelanin formation in the human substantia nigra.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Advancing AADC deficiency therapy through MR-guided multisite delivery of AAV2-hAADC to dopaminergic and serotonergic pathways in the brainstem.Molecular therapy. Advances · 2026Article
- Assessment of striatal and extrastriatal [EJNMMI research · 2026Article
- Metabolic functions for molecular chaperones and stress proteins in microcephaly.Cellular and molecular life sciences : CMLS · 2025Review
- Contribution of the dopaminergic system in toxoplasmic encephalitis neuroimmunopathogenesis.Histology and histopathology · 2025Article
- Altered Vesicular Acetylcholine Transporter Expression Regulates Acetylcholine Abundance in the Brain of Drosophila melanogaster.Journal of neurochemistry · 2025Article
- Glioblastoma multiforme: insights into pathogenesis, key signaling pathways, and therapeutic strategies.Molecular cancer · 2025Review
- Histamine synthesis and transport are coupled in axon terminals via a dual quality control system.The EMBO journal · 2024Article
- Diverse Functions of Parkin in Midbrain Dopaminergic Neurons.Movement disorders : official journal of the Movement Disorder Society · 2024Review
- Article
- Targets to Search for New Pharmacological Treatment in Idiopathic Parkinson's Disease According to the Single-Neuron Degeneration Model.Biomolecules · 2024Review
- Immobilization of Aspergillus oryzae tyrosine hydroxylase on ZnO nanocrystals for improved stability and catalytic efficiency towards L-dopa production.Scientific reports · 2023Article
- Vesicular monoamine transporter (VMAT) regional expression and roles in pathological conditions.Heliyon · 2023Review
- Dopamine Transmission Imbalance in Neuroinflammation: Perspectives on Long-Term COVID-19.International journal of molecular sciences · 2023Review
- In vivo reduction of age-dependent neuromelanin accumulation mitigates features of Parkinson's disease.Brain : a journal of neurology · 2023Article
- Regulation and modulation of biogenic amine neurotransmission inFrontiers in physiology · 2023Review
- Striatal dopamine synthesis capacity and neuromelanin in the substantia nigra: A multimodal imaging study in schizophrenia and healthy controls.Neuroscience applied · 2023Article
- Heterozygote Dopamine Transporter Knockout Rats Display Enhanced Cocaine Locomotion in Adolescent Females.International journal of molecular sciences · 2022Article
- Neuromelanin granules of the substantia nigra: proteomic profile provides links to tyrosine hydroxylase, stress granules and lysosomes.Journal of neural transmission (Vienna, Austria : 1996) · 2022Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synaptic transmission depends on neurotransmitter pools stored within vesicles that undergo regulated exocytosis. In the brain, the vesicular monoamine transporter-2 (VMAT(2)) is responsible for the loading of dopamine (DA) and other monoamines into synaptic vesicles. Prior to storage within vesicles, DA synthesis occurs at the synaptic terminal in a two-step enzymatic process. First, the rate-limiting enzyme tyrosine hydroxylase (TH) converts tyrosine to di-OH-phenylalanine. Aromatic amino acid decarboxylase (AADC) then converts di-OH-phenylalanine into DA. Here, we provide evidence that VMAT(2) physically and functionally interacts with the enzymes responsible for DA synthesis. In rat striata, TH and AADC co-immunoprecipitate with VMAT(2), whereas in PC 12 cells, TH co-immunoprecipitates with the closely related VMAT(1) and with overexpressed VMAT(2). GST pull-down assays further identified three cytosolic domains of VMAT(2) involved in the interaction with TH and AADC. Furthermore, in vitro binding assays demonstrated that TH directly interacts with VMAT(2). Additionally, using fractionation and immunoisolation approaches, we demonstrate that TH and AADC associate with VMAT(2)-containing synaptic vesicles from rat brain. These vesicles exhibited specific TH activity. Finally, the coupling between synthesis and transport of DA into vesicles was impaired in the presence of fragments involved in the VMAT(2)/TH/AADC interaction. Taken together, our results indicate that DA synthesis can occur at the synaptic vesicle membrane, where it is physically and functionally coupled to VMAT(2)-mediated transport into vesicles.
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Registered trials
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.