140581 20240321220832.0 10.1523/JNEUROSCI.1317-18.2019 doi pmid:30655355 pmid pmc:PMC6433757 pmc 0270-6474 ISSN 1529-2401 ISSN altmetric:55526003 altmetric DZNE-2020-06903 English 610 Hoffmann, Sheila P:(DE-2719)2811236 0 First author dzne Light-Activated ROS Production Induces Synaptic Autophagy. Washington, DC 2019 Soc.57413 online Crossref Society for Neuroscience 2019-01-17 print Crossref Society for Neuroscience 2019-03-20 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1677246937_7992 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote The regulated turnover of synaptic vesicle (SV) proteins is thought to involve the ubiquitin-dependent tagging and degradation through endo-lysosomal and autophagy pathways. Yet, it remains unclear which of these pathways are used, when they become activated, and whether SVs are cleared en masse together with SV proteins or whether both are degraded selectively. Equally puzzling is how quickly these systems can be activated and whether they function in real-time to support synaptic health. To address these questions, we have developed an imaging-based system that simultaneously tags presynaptic proteins while monitoring autophagy. Moreover, by tagging SV proteins with a light-activated ROS generator, Supernova, it was possible to temporally control the damage to specific SV proteins and assess their consequence to autophagy-mediated clearance mechanisms and synaptic function. Our results show that, in mouse hippocampal neurons of either sex, presynaptic autophagy can be induced in as little as 5-10 min and eliminates primarily the damaged protein rather than the SV en masse. Importantly, we also find that autophagy is essential for synaptic function, as light-activated damage to, for example, Synaptophysin only compromises synaptic function when autophagy is simultaneously blocked. These data support the concept that presynaptic boutons have a robust highly regulated clearance system to maintain not only synapse integrity, but also synaptic function.SIGNIFICANCE STATEMENT The real-time surveillance and clearance of synaptic proteins are thought to be vital to the health, functionality, and integrity of vertebrate synapses and are compromised in neurodegenerative disorders, yet the fundamental mechanisms regulating these systems remain enigmatic. Our analysis reveals that presynaptic autophagy is a critical part of a real-time clearance system at synapses capable of responding to local damage of synaptic vesicle proteins within minutes and to be critical for the ongoing functionality of these synapses. These data indicate that synapse autophagy is not only locally regulated but also crucial for the health and functionality of vertebrate presynaptic boutons. 341 - Molecular Signaling (POF3-341) G:(DE-HGF)POF3-341 POF3-341 POF III 0 2019-09-20 Crossref https://creativecommons.org/licenses/by-nc-sa/4.0/ Dataset connected to CrossRef, PubMed, Animals MeSH Autophagy: physiology MeSH Female MeSH HEK293 Cells MeSH HeLa Cells MeSH Hippocampus: metabolism MeSH Hippocampus: ultrastructure MeSH Humans MeSH Male MeSH Mice, Inbred C57BL MeSH Neurons: metabolism MeSH Neurons: ultrastructure MeSH Presynaptic Terminals: metabolism MeSH Presynaptic Terminals: ultrastructure MeSH Reactive Oxygen Species: metabolism MeSH Synaptic Vesicles: metabolism MeSH Synaptic Vesicles: ultrastructure MeSH Orlando, Marta 1 Andrzejak, Ewa P:(DE-2719)2811708 2 dzne Bruns, Christine P:(DE-2719)2811027 3 dzne Trimbuch, Thorsten 4 Rosenmund, Christian 5 Garner, Craig C P:(DE-2719)2810922 6 dzne Ackermann, Frauke P:(DE-2719)2810967 7 Last author dzne 10.1523/jneurosci.1317-18.2019 Society for Neuroscience 2019-01-17 12 2163-2183 journal-article Crossref The Journal of Neuroscience 39 2019 0270-6474 10.1523/JNEUROSCI.1317-18.2019 Vol. 39, no. 12, p. 2163 - 2183 PERI:(DE-600)1475274-8 12 39:12<2163 - 2183 2163-2183 The journal of neuroscience 39 2019 0270-6474 Pubmed Central http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433757 VDB oai:pub.dzne.de:140581 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 0 P:(DE-2719)2811236 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 2 P:(DE-2719)2811708 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)2811027 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 6 P:(DE-2719)2810922 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 7 P:(DE-2719)2810967 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-341 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Molecular Signaling 0 2019 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-13 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-13 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-13 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-13 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-13 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2022-11-13 JCR StatID:(DE-HGF)0100 StatID J NEUROSCI : 2021 2022-11-13 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2022-11-13 Peer Review StatID:(DE-HGF)0030 StatID ASC 2022-11-13 IF >= 5 StatID:(DE-HGF)9905 StatID J NEUROSCI : 2021 2022-11-13 I:(DE-2719)1810001 AG Garner Synaptopathy 0 I:(DE-2719)1813004 AG Ackermann Astrocyte - Synapse Interaction 1 journal VDB I:(DE-2719)1810001 I:(DE-2719)1813004 UNRESTRICTED 10.1083/jcb.201401070 -- missing cx 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