ArticleNature neuroscience2023
Adaptor protein AP-3 produces synaptic vesicles that release at high frequency by recruiting phospholipid flippase ATP8A1.
Article in Nature neuroscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- Synaptic vesicles that store monoamines and glutamate differ in protein composition.Science advances · 2026Article
- Phospholipid flippases ATP8A1 and ATP8A2 regulate GABAiScience · 2026Article
- Formation, Organization, and Maintenance of Synaptic Vesicle Pools: From Molecules to Structure and Dynamics.Advances in neurobiology · 2026Review
- Synaptic Vesicle Disruption in Parkinson's Disease: Dual Roles of α-Synuclein and Emerging Therapeutic Targets.Brain sciences · 2025Review
- Comparative Single-Cell Transcriptome Analysis of c-Met Receptor Expressing and Non-Expressing Projection Neurons in the Developing Frontal and Visual Cortices.Developmental neuroscience · 2025Article
- Synaptic vesicle-omics in mice captures signatures of aging and synucleinopathy.Nature communications · 2025Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Neural systems encode information in the frequency of action potentials, which is then decoded by synaptic transmission. However, the rapid, synchronous release of neurotransmitters depletes synaptic vesicles (SVs), limiting release at high firing rates. How then do synapses convey information about frequency? Here, we show in mouse hippocampal neurons and slices that the adaptor protein AP-3 makes a subset of SVs that respond specifically to high-frequency stimulation. Neurotransmitter transporters slot onto these SVs in different proportions, contributing to the distinct properties of release observed at different excitatory synapses. Proteomics reveals that AP-3 targets the phospholipid flippase ATP8A1 to SVs; loss of ATP8A1 recapitulates the defect in SV mobilization at high frequency observed with loss of AP-3. The mechanism involves recruitment of synapsin by the cytoplasmically oriented phosphatidylserine translocated by ATP8A1. Thus, ATP8A1 enables the subset of SVs made by AP-3 to release at high frequency.
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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.