Extracellular vesicle sorting of alpha-Synuclein is regulated by sumoylation

2015 | journal article; research paper. A publication with affiliation to the University of Göttingen.

Jump to: Cite & Linked | Documents & Media | Details | Version history

Cite this publication

​Extracellular vesicle sorting of alpha-Synuclein is regulated by sumoylation​
Kunadt, M.; Eckermann, K.; Stuendl, A.; Gong, J.; Russo, B.; Strauss, K. & Rai, S. et al.​ (2015) 
Acta Neuropathologica129(5) pp. 695​-713​.​ DOI: https://doi.org/10.1007/s00401-015-1408-1 

Documents & Media


Published Version

Attribution 4.0 CC BY 4.0


Kunadt, Marcel; Eckermann, Katrin; Stuendl, Anne; Gong, Jing; Russo, Belisa; Strauss, Katrin; Rai, Surya; Kügler, Sebastian ; Falomir Lockhart, Lisandro; Schwalbe, Martin; Krumova, Petranka; Oliveira, Luis M. A.; Bähr, Mathias ; Möbius, Wiebke ; Levin, Johannes; Giese, Armin; Kruse, Niels ; Mollenhauer, Brit ; Geiss‐Friedlander, Ruth ; Ludolph, Albert C.; Freischmidt, Axel; Feiler, Marisa S.; Danzer, Karin M.; Zweckstetter, Markus ; Jovin, Thomas M. ; Simons, Mikael ; Weishaupt, Jochen H. ; Schneider, Anja 
Extracellular alpha-Synuclein has been implicated in interneuronal propagation of disease pathology in Parkinson's Disease. How alpha-Synuclein is released into the extracellular space is still unclear. Here, we show that alpha-Synuclein is present in extracellular vesicles in the central nervous system. We find that sorting of alpha-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 alpha-Synuclein. We deciphered in detail the molecular mechanism which directs alpha-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.
Issue Date
Acta Neuropathologica 



Social Media