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@ARTICLE{Ogunmowo:280240,
author = {Ogunmowo, Tyler H and Hoffmann, Christian and Patel,
Chintan and Pepper, Renee and Wang, Han and Gowrisankaran,
Sindhuja and Idel, Johanna and Ho, Annie and Raychaudhuri,
Sumana and Maher, Brady J and Cooper, Benjamin H and
Milosevic, Ira and Milovanovic, Dragomir and Watanabe,
Shigeki},
title = {{I}ntersectin and endophilin condensates prime synaptic
vesicles for release site replenishment.},
journal = {Nature neuroscience},
volume = {28},
number = {8},
issn = {1097-6256},
address = {New York, NY},
publisher = {Nature America},
reportid = {DZNE-2025-00918},
pages = {1649 - 1662},
year = {2025},
abstract = {Following synaptic vesicle fusion, vacated release sites
are replenished immediately by new vesicles for subsequent
neurotransmission. These replacement vesicles are assumed to
be located near release sites and used by chance. Here we
find in mouse hippocampal excitatory synapses that
replacement vesicles are clustered near the active zone
where release sites reside by intersectin-1. Specifically,
intersectin-1 forms dynamic molecular condensates with
endophilin A1 and sequesters vesicles around this region. In
the absence of intersectin-1, fewer vesicles cluster within
20 nm of the plasma membrane, and consequently vacated sites
cannot be replenished rapidly, leading to synaptic
depression. Mutations in intersectin-1 that disrupt
endophilin A1 binding result in similar phenotypes. In the
absence of endophilin A1, intersectin-1 is mislocalized, and
this replacement pool of vesicles cannot be accessed,
suggesting that endophilin A1 is needed to mobilize these
vesicles. Thus, our work describes the replacement zone
within a synapse, where replacement vesicles are stored for
replenishment of the release site.},
keywords = {Animals / Synaptic Vesicles: metabolism / Synaptic
Vesicles: ultrastructure / Synaptic Vesicles: physiology /
Mice / Hippocampus: cytology / Hippocampus: metabolism /
Adaptor Proteins, Vesicular Transport: metabolism / Adaptor
Proteins, Vesicular Transport: genetics / Synapses:
metabolism / Synapses: ultrastructure / Neurons / Adaptor
Proteins, Signal Transducing: metabolism / Adaptor Proteins,
Signal Transducing: genetics / Synaptic Transmission:
physiology / Mice, Inbred C57BL / Mutation: genetics /
Adaptor Proteins, Vesicular Transport (NLM Chemicals) /
intersectin 1 (NLM Chemicals) / endophilin A1 protein, mouse
(NLM Chemicals) / Adaptor Proteins, Signal Transducing (NLM
Chemicals)},
cin = {AG Milovanovic (Berlin) / AG Milovanovic (Bonn)},
ddc = {610},
cid = {I:(DE-2719)1813002 / I:(DE-2719)1013043},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40629141},
pmc = {pmc:PMC12321584},
doi = {10.1038/s41593-025-02002-4},
url = {https://pub.dzne.de/record/280240},
}