Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation

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 fin...

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Detalles Bibliográficos
Autores principales: Kunadt, Marcel, Eckermann, Katrin, Stuendl, Anne, Gong, Jing, Russo, Belisa, Strauss, Katrin, Rai, Surya, Kügler, Sebastian, Falomir Lockhart, Lisandro Jorge, 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
Formato: Articulo
Lenguaje:Inglés
Publicado: 2015
Materias:
Biología
Ciencias Médicas
Exosomes
Spreading
Sumoylation
α-Synuclein
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/104738
http://hdl.handle.net/11336/51660
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-104738
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Ciencias Médicas
Exosomes
Spreading
Sumoylation
α-Synuclein
spellingShingle Biología
Ciencias Médicas
Exosomes
Spreading
Sumoylation
α-Synuclein
Kunadt, Marcel
Eckermann, Katrin
Stuendl, Anne
Gong, Jing
Russo, Belisa
Strauss, Katrin
Rai, Surya
Kügler, Sebastian
Falomir Lockhart, Lisandro Jorge
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 vesicle sorting of α-Synuclein is regulated by sumoylation
topic_facet Biología
Ciencias Médicas
Exosomes
Spreading
Sumoylation
α-Synuclein
description 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.
format Articulo
Articulo
author Kunadt, Marcel
Eckermann, Katrin
Stuendl, Anne
Gong, Jing
Russo, Belisa
Strauss, Katrin
Rai, Surya
Kügler, Sebastian
Falomir Lockhart, Lisandro Jorge
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
author_facet Kunadt, Marcel
Eckermann, Katrin
Stuendl, Anne
Gong, Jing
Russo, Belisa
Strauss, Katrin
Rai, Surya
Kügler, Sebastian
Falomir Lockhart, Lisandro Jorge
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
author_sort Kunadt, Marcel
title Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation
title_short Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation
title_full Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation
title_fullStr Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation
title_full_unstemmed Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation
title_sort extracellular vesicle sorting of α-synuclein is regulated by sumoylation
publishDate 2015
url http://sedici.unlp.edu.ar/handle/10915/104738
http://hdl.handle.net/11336/51660
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