NDLI: Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation

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Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation

Content Provider	PubMed Central
Author	Marcel, Kunadt Eckermann, Katrin Anne, Stuendl Gong, Jing Russo, Belisa Strauss, Katrin Rai, Surya Kügler, Sebastian Lockhart, Lisandro Falomir Schwalbe, Martin Krumova, Petranka Oliveira, Luis M. A. Bähr, Mathias Möbius, Wiebke Levin, Johannes Giese, Armin Kruse, Niels Mollenhauer, Brit Ruth, Geiss-friedlander Ludolph, Albert C. Freischmidt, Axel Feiler, Marisa S. Danzer, Karin M. Markus, Zweckstetter Jovin, Thomas M. Simons, Mikael Weishaupt, Jochen H. Schneider, Anja
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.
Related Links	http://dx.doi.org/10.1007/s00401-015-1408-1
Ending Page	713
Page Count	19
Starting Page	695
File Format	PDF
ISSN	00016322
e-ISSN	14320533
Journal	Acta Neuropathologica
Issue Number	5
Volume Number	129
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2015-05-01
Access Restriction	Open
Rights Holder	Springer Berlin Heidelberg
Subject Keyword	Pathology and Forensic Medicine Cellular and Molecular Neuroscience Clinical Neurology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neurology (clinical) Pathology and Forensic Medicine Cellular and Molecular Neuroscience

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