ArticleProceedings of the National Academy of Sciences of the United States of America2023
Adaptor protein-3 produces synaptic vesicles that release phasic dopamine.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- The Synaptic Vesicle Priming Protein Munc13 Mediates Evoked Somatodendritic Dopamine Release.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Synaptic vesicles that store monoamines and glutamate differ in protein composition.Science advances · 2026Article
- Impact of distinct neurotransmitter release modes on neuronal signaling.Molecular psychiatry · 2026Review
- IGF-like growth factors that couple food sensing to developmental decisions employ different release mechanisms in a single pair ofbioRxiv : the preprint server for biology · 2026Article
- The synaptic vesicle priming protein Munc13 mediates evoked somatodendritic dopamine release.bioRxiv : the preprint server for biology · 2025Article
- Synaptic Vesicle Disruption in Parkinson's Disease: Dual Roles of α-Synuclein and Emerging Therapeutic Targets.Brain sciences · 2025Review
- Article
- Transcriptomic Profile of the Male Rat Hypothalamus and Nucleus Accumbens After Paroxetine Treatment and Withdrawal: Possible Causes of Sexual Dysfunction.Molecular neurobiology · 2025Article
- Action Potential Firing Patterns Regulate Dopamine Release via Voltage-Sensitive Dopamine D2 Autoreceptors in Mouse Striatum In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Synaptic vesicle characterization of iPSC-derived dopaminergic neurons provides insight into distinct secretory vesicle pools.NPJ Parkinson's disease · 2025Article
- Case Report: Subacute combined degeneration of the spinal cord mimic accompanying adaptor protein-3B2-IgG.Frontiers in immunology · 2025Article
- Article
- Adaptor protein-3 produces synaptic vesicles that release phasic dopamine.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A voyage from the ER: spatiotemporal insights into polarized protein secretion in neurons.Frontiers in cell and developmental biology · 2023Article
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Authors and funding
11 authors at 3 institutions in 1 country.
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Abstract
The burst firing of midbrain dopamine neurons releases a phasic dopamine signal that mediates reinforcement learning. At many synapses, however, high firing rates deplete synaptic vesicles (SVs), resulting in synaptic depression that limits release. What accounts for the increased release of dopamine by stimulation at high frequency? We find that adaptor protein-3 (AP-3) and its coat protein VPS41 promote axonal dopamine release by targeting vesicular monoamine transporter VMAT2 to the axon rather than dendrites. AP-3 and VPS41 also produce SVs that respond preferentially to high-frequency stimulation, independent of their role in axonal polarity. In addition, conditional inactivation of VPS41 in dopamine neurons impairs reinforcement learning, and this involves a defect in the frequency dependence of release rather than the amount of dopamine released. Thus, AP-3 and VPS41 promote the axonal polarity of dopamine release but enable learning by producing a distinct population of SVs tuned specifically to high firing frequency that confers the phasic release of dopamine.
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