280240 20250831001814.0 10.1038/s41593-025-02002-4 doi pmid:40629141 pmid pmc:PMC12321584 pmc 1097-6256 ISSN 1546-1726 ISSN altmetric:179085987 altmetric DZNE-2025-00918 English 610 Ogunmowo, Tyler H 0 Intersectin and endophilin condensates prime synaptic vesicles for release site replenishment. New York, NY 2025 Nature America article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1756201305_31524 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote 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. 351 - Brain Function (POF4-351) G:(DE-HGF)POF4-351 POF4-351 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Adaptor Proteins, Vesicular Transport NLM Chemicals intersectin 1 NLM Chemicals endophilin A1 protein, mouse NLM Chemicals Adaptor Proteins, Signal Transducing NLM Chemicals Animals MeSH Synaptic Vesicles: metabolism MeSH Synaptic Vesicles: ultrastructure MeSH Synaptic Vesicles: physiology MeSH Mice MeSH Hippocampus: cytology MeSH Hippocampus: metabolism MeSH Adaptor Proteins, Vesicular Transport: metabolism MeSH Adaptor Proteins, Vesicular Transport: genetics MeSH Synapses: metabolism MeSH Synapses: ultrastructure MeSH Neurons MeSH Adaptor Proteins, Signal Transducing: metabolism MeSH Adaptor Proteins, Signal Transducing: genetics MeSH Synaptic Transmission: physiology MeSH Mice, Inbred C57BL MeSH Mutation: genetics MeSH Hoffmann, Christian P:(DE-2719)9000582 1 First author dzne Patel, Chintan 0000-0001-6245-2406 2 Pepper, Renee 3 Wang, Han P:(DE-2719)9001572 4 First author Gowrisankaran, Sindhuja 5 Idel, Johanna 6 Ho, Annie 0009-0004-9724-9853 7 Raychaudhuri, Sumana 8 Maher, Brady J 0000-0001-5930-885X 9 Cooper, Benjamin H 0000-0003-2374-9922 10 Milosevic, Ira 0000-0001-6440-3763 11 Milovanovic, Dragomir P:(DE-2719)9000670 12 Watanabe, Shigeki 0000-0001-7580-8141 13 10.1038/s41593-025-02002-4 Vol. 28, no. 8, p. 1649 - 1662 PERI:(DE-600)1494955-6 8 1649 - 1662 Nature neuroscience 28 2025 1097-6256 http://pub.dzne.de/record/280240/files/DZNE-2025-00918%20SUP%2BSRC.zip OpenAccess http://pub.dzne.de/record/280240/files/DZNE-2025-00918.pdf OpenAccess pdfa http://pub.dzne.de/record/280240/files/DZNE-2025-00918.pdf?subformat=pdfa oai:pub.dzne.de:280240 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 1 P:(DE-2719)9000582 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 4 P:(DE-2719)9001572 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 12 P:(DE-2719)9000670 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-351 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Brain Function 0 2025 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2025-01-07 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2025-01-07 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2025-01-07 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2025-01-07 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2025-01-07 JCR StatID:(DE-HGF)0100 StatID NAT NEUROSCI : 2022 2025-01-07 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2025-01-07 DEAL Nature StatID:(DE-HGF)3003 StatID 2025-01-07 ger WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2025-01-07 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2025-01-07 OpenAccess StatID:(DE-HGF)0510 StatID Peer Review StatID:(DE-HGF)0030 StatID ASC 2025-01-07 IF >= 25 StatID:(DE-HGF)9925 StatID NAT NEUROSCI : 2022 2025-01-07 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2025-01-07 Creative Commons Attribution CC BY 4.0 LIC:(DE-HGF)CCBY4 HGFVOC Nationallizenz StatID:(DE-HGF)0420 StatID 2025-01-07 ger DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2025-01-07 I:(DE-2719)1813002 AG Milovanovic (Berlin) Molecular Neuroscience 0 I:(DE-2719)1013043 AG Milovanovic (Bonn) Molecular Neuroscience 1 journal VDB UNRESTRICTED I:(DE-2719)1813002 I:(DE-2719)1013043 FullTexts