Adaptor protein AP-3 produces synaptic vesicles that release at high frequency by recruiting phospholipid flippase ATP8A1
Issued Date
2023-01-01
Resource Type
ISSN
10976256
eISSN
15461726
Scopus ID
2-s2.0-85171363587
Journal Title
Nature Neuroscience
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Neuroscience (2023)
Suggested Citation
Xu H. Adaptor protein AP-3 produces synaptic vesicles that release at high frequency by recruiting phospholipid flippase ATP8A1. Nature Neuroscience (2023). doi:10.1038/s41593-023-01434-0 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/90198
Title
Adaptor protein AP-3 produces synaptic vesicles that release at high frequency by recruiting phospholipid flippase ATP8A1
Author(s)
Author's Affiliation
Other Contributor(s)
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.