Adaptor protein AP-3 produces synaptic vesicles that release at high frequency by recruiting phospholipid flippase ATP8A1.
Journal
Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
04
01
2023
accepted:
14
08
2023
medline:
4
10
2023
pubmed:
19
9
2023
entrez:
18
9
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37723322
doi: 10.1038/s41593-023-01434-0
pii: 10.1038/s41593-023-01434-0
doi:
Substances chimiques
Phospholipids
0
Synapsins
0
Ap3b1 protein, mouse
0
Atp8a1 protein, mouse
EC 3.6.1.3
Adaptor Protein Complex 3
0
Adenosine Triphosphatases
EC 3.6.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1685-1700Subventions
Organisme : NINDS NIH HHS
ID : R01 NS103938
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS103938
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH050712
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS103938
Pays : United States
Organisme : NIH HHS
ID : S10 OD017993
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
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