255148 20230726100418.0 10.1101/440719 doi altmetric:49522831 altmetric DZNE-2023-00264 Hoffmann, Sheila P:(DE-2719)2811236 0 First author dzne Light induced synaptic vesicle autophagy 2018 Preprint preprint preprint PUB:(DE-HGF)25 1678100177_13063 PUB:(DE-HGF) WORKING_PAPER ORCID Electronic Article 28 EndNote preprint DRIVER ARTICLE BibTeX Output Types/Working Paper DataCite 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-mass 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 reactive oxygen species (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, presynaptic autophagy can be induced in as little as 5-10 minutes and eliminates primarily the damaged protein rather than the SV en-mass. Importantly, we also find that autophagy is essential for synaptic function, as light-induced damage to e.g. 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. 899 - ohne Topic (POF4-899) G:(DE-HGF)POF4-899 POF4-899 POF IV 0 Dataset connected to CrossRef Orlando, Marta 1 Andrzejak, Ewa P:(DE-2719)2811708 2 dzne Trimbuch, Thorsten 3 Rosenmund, Christian 4 Ackermann, Frauke P:(DE-2719)2810967 5 dzne Garner, Craig C. P:(DE-2719)2810922 6 Last author dzne 10.1101/440719 Hoffmann, Sheila et.al. Washington, DC : Soc.57413, 2019 RelatedTo DZNE-2020-06903 Light-Activated ROS Production Induces Synaptic Autophagy. oai:pub.dzne.de:255148 VDB 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 5 P:(DE-2719)2810967 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 6 P:(DE-2719)2810922 DE-HGF Programmungebundene Forschung ohne Programm G:(DE-HGF)POF4-890 G:(DE-HGF)POF4-899 G:(DE-HGF)POF4 G:(DE-HGF)POF4-800 G:(DE-HGF)POF ohne Topic 0 2018 I:(DE-2719)1810001 AG Garner Synaptopathy 0 I:(DE-2719)1813004 AG Ackermann Astrocyte - Synapse Interaction 1 preprint VDB I:(DE-2719)1810001 I:(DE-2719)1813004 UNRESTRICTED