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@ARTICLE{Kunadt:137883,
      author       = {Kunadt, Marcel and Eckermann, Katrin and Stuendl, Anne and
                      Gong, Jing and Russo, Belisa and Strauss, Katrin and Rai,
                      Surya and Kügler, Sebastian and Falomir Lockhart, Lisandro
                      and Schwalbe, Martin and Krumova, Petranka and Oliveira,
                      Luis M A and Bähr, Mathias and Möbius, Wiebke and Levin,
                      Johannes and Giese, Armin and Kruse, Niels and Mollenhauer,
                      Brit and Geiss-Friedlander, Ruth and Ludolph, Albert C and
                      Freischmidt, Axel and Feiler, Marisa S and Danzer, Karin M
                      and Zweckstetter, Markus and Jovin, Thomas M and Simons,
                      Mikael and Weishaupt, Jochen H and Schneider, Anja},
      title        = {{E}xtracellular vesicle sorting of α-{S}ynuclein is
                      regulated by sumoylation.},
      journal      = {Acta neuropathologica},
      volume       = {129},
      number       = {5},
      issn         = {0001-6322},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DZNE-2020-04205},
      pages        = {695-713},
      year         = {2015},
      abstract     = {Extracellular α-Synuclein has been implicated in
                      interneuronal propagation of disease pathology in
                      Parkinson's Disease. How α-Synuclein is released into the
                      extracellular space is still unclear. Here, we show that
                      α-Synuclein is present in extracellular vesicles in the
                      central nervous system. We find that sorting of α-Synuclein
                      in extracellular vesicles is regulated by sumoylation and
                      that sumoylation acts as a sorting factor for targeting of
                      both, cytosolic and transmembrane proteins, to extracellular
                      vesicles. We provide evidence that the SUMO-dependent
                      sorting utilizes the endosomal sorting complex required for
                      transport (ESCRT) by interaction with phosphoinositols.
                      Ubiquitination of cargo proteins is so far the only known
                      determinant for ESCRT-dependent sorting into the
                      extracellular vesicle pathway. Our study reveals a function
                      of SUMO protein modification as a Ubiquitin-independent
                      ESCRT sorting signal, regulating the extracellular vesicle
                      release of α-Synuclein. We deciphered in detail the
                      molecular mechanism which directs α-Synuclein into
                      extracellular vesicles which is of highest relevance for the
                      understanding of Parkinson's disease pathogenesis and
                      progression at the molecular level. We furthermore propose
                      that sumo-dependent sorting constitutes a mechanism with
                      more general implications for cell biology.},
      keywords     = {Animals / Cell Culture Techniques / Cell Line, Tumor /
                      Endosomal Sorting Complexes Required for Transport: genetics
                      / Endosomal Sorting Complexes Required for Transport:
                      metabolism / Extracellular Vesicles: genetics /
                      Extracellular Vesicles: metabolism / Mice / Oligodendroglia:
                      cytology / Oligodendroglia: metabolism / SUMO-1 Protein:
                      genetics / SUMO-1 Protein: metabolism / Signal Transduction:
                      genetics / Signal Transduction: physiology / Sumoylation:
                      physiology / alpha-Synuclein: genetics / alpha-Synuclein:
                      metabolism / Endosomal Sorting Complexes Required for
                      Transport (NLM Chemicals) / SUMO-1 Protein (NLM Chemicals) /
                      alpha-Synuclein (NLM Chemicals)},
      cin          = {AG Schneider Göttingen / AG Zweckstetter},
      ddc          = {610},
      cid          = {I:(DE-2719)1440011 / I:(DE-2719)1410001},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342) / 344
                      - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-342 / G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25778619},
      pmc          = {pmc:PMC4405286},
      doi          = {10.1007/s00401-015-1408-1},
      url          = {https://pub.dzne.de/record/137883},
}