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Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation

Overview of attention for article published in Acta Neuropathologica, March 2015
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Title
Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation
Published in
Acta Neuropathologica, March 2015
DOI 10.1007/s00401-015-1408-1
Pubmed ID
Authors

Marcel Kunadt, Katrin Eckermann, Anne Stuendl, Jing Gong, Belisa Russo, Katrin Strauss, Surya Rai, Sebastian Kügler, Lisandro Falomir Lockhart, Martin Schwalbe, Petranka Krumova, Luis M. A. Oliveira, Mathias Bähr, Wiebke Möbius, Johannes Levin, Armin Giese, Niels Kruse, Brit Mollenhauer, Ruth Geiss-Friedlander, Albert C. Ludolph, Axel Freischmidt, Marisa S. Feiler, Karin M. Danzer, Markus Zweckstetter, Thomas M. Jovin, Mikael Simons, Jochen H. Weishaupt, Anja Schneider

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.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 192 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Netherlands 1 <1%
Unknown 191 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 41 21%
Researcher 25 13%
Student > Bachelor 21 11%
Student > Master 20 10%
Student > Doctoral Student 13 7%
Other 26 14%
Unknown 46 24%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 47 24%
Agricultural and Biological Sciences 43 22%
Neuroscience 24 13%
Medicine and Dentistry 11 6%
Immunology and Microbiology 6 3%
Other 13 7%
Unknown 48 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 January 2016.
All research outputs
#13,938,371
of 22,796,179 outputs
Outputs from Acta Neuropathologica
#2,040
of 2,369 outputs
Outputs of similar age
#145,948
of 286,347 outputs
Outputs of similar age from Acta Neuropathologica
#23
of 30 outputs
Altmetric has tracked 22,796,179 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,369 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.3. This one is in the 13th percentile – i.e., 13% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 286,347 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 47th percentile – i.e., 47% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 30 others from the same source and published within six weeks on either side of this one. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.