%0 Journal Article
%A Kunadt, Marcel
%A Eckermann, Katrin
%A Stuendl, Anne
%A Gong, Jing
%A Russo, Belisa
%A Strauss, Katrin
%A Rai, Surya
%A Kügler, Sebastian
%A Falomir Lockhart, Lisandro
%A Schwalbe, Martin
%A Krumova, Petranka
%A Oliveira, Luis M A
%A Bähr, Mathias
%A Möbius, Wiebke
%A Levin, Johannes
%A Giese, Armin
%A Kruse, Niels
%A Mollenhauer, Brit
%A Geiss-Friedlander, Ruth
%A Ludolph, Albert C
%A Freischmidt, Axel
%A Feiler, Marisa S
%A Danzer, Karin M
%A Zweckstetter, Markus
%A Jovin, Thomas M
%A Simons, Mikael
%A Weishaupt, Jochen H
%A Schneider, Anja
%T Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation.
%J Acta neuropathologica
%V 129
%N 5
%@ 0001-6322
%C Heidelberg
%I Springer
%M DZNE-2020-04205
%P 695-713
%D 2015
%X 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.
%K Animals
%K Cell Culture Techniques
%K Cell Line, Tumor
%K Endosomal Sorting Complexes Required for Transport: genetics
%K Endosomal Sorting Complexes Required for Transport: metabolism
%K Extracellular Vesicles: genetics
%K Extracellular Vesicles: metabolism
%K Mice
%K Oligodendroglia: cytology
%K Oligodendroglia: metabolism
%K SUMO-1 Protein: genetics
%K SUMO-1 Protein: metabolism
%K Signal Transduction: genetics
%K Signal Transduction: physiology
%K Sumoylation: physiology
%K alpha-Synuclein: genetics
%K alpha-Synuclein: metabolism
%K Endosomal Sorting Complexes Required for Transport (NLM Chemicals)
%K SUMO-1 Protein (NLM Chemicals)
%K alpha-Synuclein (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:25778619
%2 pmc:PMC4405286
%R 10.1007/s00401-015-1408-1
%U https://pub.dzne.de/record/137883