Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation

dc.creatorKunadt, Marcel
dc.creatorEckermann, Katrin
dc.creatorStuendl, Anne
dc.creatorGong, Jing
dc.creatorRusso, Belisa
dc.creatorStrauss, Katrin
dc.creatorRai, Surya
dc.creatorKügler, Sebastian
dc.creatorFalomir Lockhart, Lisandro Jorge
dc.creatorSchwalbe, Martin
dc.creatorKrumova, Petranka
dc.creatorOliveira, Luis M. A.
dc.creatorBähr, Mathias
dc.creatorMöbius, Wiebke
dc.creatorLevin, Johannes
dc.creatorGiese, Armin
dc.creatorKruse, Niels
dc.creatorMollenhauer, Brit
dc.creatorGeiss Friedlander, Ruth
dc.creatorLudolph, Albert C.
dc.creatorFreischmidt, Axel
dc.creatorFeiler, Marisa S.
dc.creatorDanzer, Karin M.
dc.creatorZweckstetter, Markus
dc.creatorJovin, Thomas M.
dc.creatorSimons, Mikael
dc.creatorWeishaupt, Jochen H.
dc.creatorSchneider, Anja
dc.date2015-05
dc.date2020-09-16T12:57:00Z
dc.date.accessioned2023-07-14T21:57:39Z
dc.date.available2023-07-14T21:57:39Z
dc.identifierhttp://sedici.unlp.edu.ar/handle/10915/104738
dc.identifierhttp://hdl.handle.net/11336/51660
dc.identifierissn:1432-0533
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/7445067
dc.descriptionExtracellular 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.
dc.descriptionInstituto de Investigaciones Bioquímicas de La Plata
dc.formatapplication/pdf
dc.format695-713
dc.languageen
dc.rightshttp://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.subjectBiología
dc.subjectCiencias Médicas
dc.subjectExosomes
dc.subjectSpreading
dc.subjectSumoylation
dc.subjectα-Synuclein
dc.titleExtracellular vesicle sorting of α-Synuclein is regulated by sumoylation
dc.typeArticulo
dc.typeArticulo


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