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@ARTICLE{Hoffmann:255148,
      author       = {Hoffmann, Sheila and Orlando, Marta and Andrzejak, Ewa and
                      Trimbuch, Thorsten and Rosenmund, Christian and Ackermann,
                      Frauke and Garner, Craig C.},
      title        = {{L}ight induced synaptic vesicle autophagy},
      reportid     = {DZNE-2023-00264},
      year         = {2018},
      abstract     = {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.},
      cin          = {AG Garner / AG Ackermann},
      cid          = {I:(DE-2719)1810001 / I:(DE-2719)1813004},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)25},
      doi          = {10.1101/440719},
      url          = {https://pub.dzne.de/record/255148},
}