001     255148
005     20230726100418.0
024 7 _ |a 10.1101/440719
|2 doi
024 7 _ |a altmetric:49522831
|2 altmetric
037 _ _ |a DZNE-2023-00264
100 1 _ |a Hoffmann, Sheila
|0 P:(DE-2719)2811236
|b 0
|e First author
|u dzne
245 _ _ |a Light induced synaptic vesicle autophagy
260 _ _ |c 2018
336 7 _ |a Preprint
|b preprint
|m preprint
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|s 1678100177_13063
|2 PUB:(DE-HGF)
336 7 _ |a WORKING_PAPER
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336 7 _ |a Electronic Article
|0 28
|2 EndNote
336 7 _ |a preprint
|2 DRIVER
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a Output Types/Working Paper
|2 DataCite
520 _ _ |a 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.
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588 _ _ |a Dataset connected to CrossRef
700 1 _ |a Orlando, Marta
|b 1
700 1 _ |a Andrzejak, Ewa
|0 P:(DE-2719)2811708
|b 2
|u dzne
700 1 _ |a Trimbuch, Thorsten
|b 3
700 1 _ |a Rosenmund, Christian
|b 4
700 1 _ |a Ackermann, Frauke
|0 P:(DE-2719)2810967
|b 5
|u dzne
700 1 _ |a Garner, Craig C.
|0 P:(DE-2719)2810922
|b 6
|e Last author
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773 _ _ |a 10.1101/440719
787 0 _ |a Hoffmann, Sheila et.al.
|d Washington, DC : Soc.57413, 2019
|i RelatedTo
|0 DZNE-2020-06903
|r
|t Light-Activated ROS Production Induces Synaptic Autophagy.
909 C O |o oai:pub.dzne.de:255148
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
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913 1 _ |a DE-HGF
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914 1 _ |y 2018
920 1 _ |0 I:(DE-2719)1810001
|k AG Garner
|l Synaptopathy
|x 0
920 1 _ |0 I:(DE-2719)1813004
|k AG Ackermann
|l Astrocyte - Synapse Interaction
|x 1
980 _ _ |a preprint
980 _ _ |a VDB
980 _ _ |a I:(DE-2719)1810001
980 _ _ |a I:(DE-2719)1813004
980 _ _ |a UNRESTRICTED


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