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000137883 037__ $$aDZNE-2020-04205
000137883 041__ $$aEnglish
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000137883 1001_ $$aKunadt, Marcel$$b0
000137883 245__ $$aExtracellular vesicle sorting of α-Synuclein is regulated by sumoylation.
000137883 260__ $$aHeidelberg$$bSpringer$$c2015
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000137883 520__ $$aExtracellular α-Synuclein has been implicated in interneuronal propagation of disease pathology in Parkinson's Disease. How α-Synuclein is released into the extracellular space is still unclear. Here, we show that α-Synuclein is present in extracellular vesicles in the central nervous system. We find that sorting of α-Synuclein in extracellular vesicles is regulated by sumoylation and that sumoylation acts as a sorting factor for targeting of both, cytosolic and transmembrane proteins, to extracellular vesicles. We provide evidence that the SUMO-dependent sorting utilizes the endosomal sorting complex required for transport (ESCRT) by interaction with phosphoinositols. Ubiquitination of cargo proteins is so far the only known determinant for ESCRT-dependent sorting into the extracellular vesicle pathway. Our study reveals a function of SUMO protein modification as a Ubiquitin-independent ESCRT sorting signal, regulating the extracellular vesicle release of α-Synuclein. We deciphered in detail the molecular mechanism which directs α-Synuclein into extracellular vesicles which is of highest relevance for the understanding of Parkinson's disease pathogenesis and progression at the molecular level. We furthermore propose that sumo-dependent sorting constitutes a mechanism with more general implications for cell biology.
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000137883 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x1
000137883 542__ $$2Crossref$$i2015-03-17$$uhttp://creativecommons.org/licenses/by/4.0
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000137883 650_7 $$2NLM Chemicals$$aEndosomal Sorting Complexes Required for Transport
000137883 650_7 $$2NLM Chemicals$$aSUMO-1 Protein
000137883 650_7 $$2NLM Chemicals$$aalpha-Synuclein
000137883 650_2 $$2MeSH$$aAnimals
000137883 650_2 $$2MeSH$$aCell Culture Techniques
000137883 650_2 $$2MeSH$$aCell Line, Tumor
000137883 650_2 $$2MeSH$$aEndosomal Sorting Complexes Required for Transport: genetics
000137883 650_2 $$2MeSH$$aEndosomal Sorting Complexes Required for Transport: metabolism
000137883 650_2 $$2MeSH$$aExtracellular Vesicles: genetics
000137883 650_2 $$2MeSH$$aExtracellular Vesicles: metabolism
000137883 650_2 $$2MeSH$$aMice
000137883 650_2 $$2MeSH$$aOligodendroglia: cytology
000137883 650_2 $$2MeSH$$aOligodendroglia: metabolism
000137883 650_2 $$2MeSH$$aSUMO-1 Protein: genetics
000137883 650_2 $$2MeSH$$aSUMO-1 Protein: metabolism
000137883 650_2 $$2MeSH$$aSignal Transduction: genetics
000137883 650_2 $$2MeSH$$aSignal Transduction: physiology
000137883 650_2 $$2MeSH$$aSumoylation: physiology
000137883 650_2 $$2MeSH$$aalpha-Synuclein: genetics
000137883 650_2 $$2MeSH$$aalpha-Synuclein: metabolism
000137883 7001_ $$aEckermann, Katrin$$b1
000137883 7001_ $$aStuendl, Anne$$b2
000137883 7001_ $$0P:(DE-2719)2812450$$aGong, Jing$$b3
000137883 7001_ $$0P:(DE-2719)2811238$$aRusso, Belisa$$b4
000137883 7001_ $$aStrauss, Katrin$$b5
000137883 7001_ $$aRai, Surya$$b6
000137883 7001_ $$aKügler, Sebastian$$b7
000137883 7001_ $$aFalomir Lockhart, Lisandro$$b8
000137883 7001_ $$0P:(DE-HGF)0$$aSchwalbe, Martin$$b9
000137883 7001_ $$aKrumova, Petranka$$b10
000137883 7001_ $$aOliveira, Luis M A$$b11
000137883 7001_ $$0P:(DE-HGF)0$$aBähr, Mathias$$b12
000137883 7001_ $$aMöbius, Wiebke$$b13
000137883 7001_ $$0P:(DE-HGF)0$$aLevin, Johannes$$b14
000137883 7001_ $$0P:(DE-HGF)0$$aGiese, Armin$$b15
000137883 7001_ $$aKruse, Niels$$b16
000137883 7001_ $$0P:(DE-2719)9001340$$aMollenhauer, Brit$$b17$$udzne
000137883 7001_ $$aGeiss-Friedlander, Ruth$$b18
000137883 7001_ $$0P:(DE-HGF)0$$aLudolph, Albert C$$b19
000137883 7001_ $$0P:(DE-HGF)0$$aFreischmidt, Axel$$b20
000137883 7001_ $$aFeiler, Marisa S$$b21
000137883 7001_ $$0P:(DE-2719)9001513$$aDanzer, Karin M$$b22$$udzne
000137883 7001_ $$0P:(DE-2719)2810591$$aZweckstetter, Markus$$b23
000137883 7001_ $$aJovin, Thomas M$$b24
000137883 7001_ $$0P:(DE-HGF)0$$aSimons, Mikael$$b25
000137883 7001_ $$0P:(DE-HGF)0$$aWeishaupt, Jochen H$$b26
000137883 7001_ $$0P:(DE-2719)2812035$$aSchneider, Anja$$b27$$eLast author
000137883 77318 $$2Crossref$$3journal-article$$a10.1007/s00401-015-1408-1$$b : Springer Science and Business Media LLC, 2015-03-17$$n5$$p695-713$$tActa Neuropathologica$$v129$$x0001-6322$$y2015
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000137883 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405286
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