Deployment of endocytic machinery to periactive zones of nerve terminals is independent of active zone assembly and evoked release
Year: 2026
Type: article
Abstract: 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 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.
Source: eLife
Authors: Javier Emperador-Melero, Steven J Del Signore, Kevin M De León González, Pascal S Kaeser, Avital Adah Rodal
Institutions: Harvard University, Brandeis University
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: Bioinspired Soft Materials, Abberior 3D-STED microscope for super-resolution imaging, G6022841445, G7410890623, G7449103793, G7818429754, G7833242660, Molecular Mechanisms for Co‐Assembly of Endocytic and Exocytic Machineries at a Synapse, G9000013280, G9000089312, G9000124203, Bloomington Drosophila Stock Center at Indiana University, Dissecting the assembly of neurotransmitter release sites
OpenAlex ID: W4409852872