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Review
. 2025 Oct;603(20):5889-5901.
doi: 10.1113/JP286179. Epub 2024 Jul 21.

Role of adaptor protein complexes in generating functionally distinct synaptic vesicle pools

Hrach Asmerian  1   2   3 , Jacob Alberts  1   2   3 , Anna M Sanetra  1   2   3 , Alexia J Diaz  1   2   3 , Katlin Silm  1   2   3
Affiliations
Review

Role of adaptor protein complexes in generating functionally distinct synaptic vesicle pools

Hrach Asmerian et al. J Physiol. 2025 Oct.

Abstract

The synaptic vesicle (SV) cycle ensures the release of neurotransmitters and the replenishment of SVs to sustain neuronal activity. Multiple endocytosis and sorting pathways contribute to the recapture of the SV membrane and proteins after fusion. Adaptor protein (AP) complexes are among the critical components of the SV retrieval machinery. The canonical clathrin adaptor AP2 ensures the replenishment of most SVs across many neuronal populations. An alternative AP1/AP3-dependent process mediates the formation of a subset of SVs that differ from AP2 vesicles in molecular composition and respond preferentially during higher frequency firing. Furthermore, recent studies show that vesicular transporters for different neurotransmitters depend to a different extent on the AP3 pathway and this affects the release properties of the respective neurotransmitters. This review focuses on the current understanding of the AP-dependent molecular and functional diversity among SVs. We also discuss the contribution of these pathways to the regulation of neurotransmitter release across neuronal populations.

Keywords: adaptor protein complexes; neurotransmitter release; synaptic vesicle pools.

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