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Deployment of endocytic machinery to periactive zones of nerve terminals is independent of active zone assembly and evoked release
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Deployment of endocytic machinery to periactive zones of nerve terminals is independent of active zone assembly and evoked release

Javier Emperador-Melero, Steven J Del Signore, Kevin M De León González, Pascal S Kaeser and Avital Rodal
eLife
eLife
06/23/2025
Handle:
https://hdl.handle.net/10192/79113

Abstract

Neuroscience

reviewed preprint

In presynaptic nerve terminals, the endocytic apparatus rapidly restores synaptic vesicles after neurotransmitter release. Many endocytic proteins localize to the periactive zone, a loosely defined area adjacent to active zones. A prevailing model posits that recruitment of these endocytic proteins to the periactive zone is activity-dependent. We here show that periactive zone targeting of endocytic proteins is largely independent of active zone machinery and synaptic activity. At mouse hippocampal synapses and Drosophila neuromuscular junctions, pharmacological or genetic silencing resulted in unchanged or increased levels of endocytic proteins including Dynamin, Amphiphysin, Nervous Wreck, Endophilin A, Dap160/Intersectin, PIPK1γ and AP-180. Similarly, disruption of active zone assembly via genetic ablation of active zone scaffolds at each synapse did not impair the localization of endocytic proteins. Overall, our work indicates that endocytic proteins are constitutively deployed to the periactive zone and supports the existence of independent assembly pathways for active zones and periactive zones.
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