Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation
- Autores
- 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
- Año de publicación
- 2015
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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.
Fil: Kunadt, Marcel. Universität Göttingen; Alemania. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania. Max-Planck-Institute for Experimental Medicine; Alemania
Fil: Eckermann, Katrin. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania
Fil: Stuendl, Anne. Universität Göttingen; Alemania
Fil: Gong, Jing. Max-Planck-Institute for Experimental Medicine; Alemania
Fil: Russo, Belisa. Max-Planck-Institute for Experimental Medicine; Alemania
Fil: Strauss, Katrin. Universität Göttingen; Alemania. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania
Fil: Rai, Surya. Universität Göttingen; Alemania
Fil: Kügler, Sebastian. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania
Fil: Falomir Lockhart, Lisandro Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina. Max-Planck-Institute for Biophysical Chemistry; Alemania
Fil: Schwalbe, Martin. Max-Planck-Institute for Biophysical Chemistry; Alemania
Fil: Krumova, Petranka. University Medicine Göttingen; Alemania
Fil: Oliveira, Luis M. A.. Max-Planck-Institute for Biophysical Chemistry; Alemania
Fil: Bähr, Mathias. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania
Fil: Möbius, Wiebke. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania
Fil: Levin, Johannes. Ludwig-Maximilians-University; Alemania
Fil: Giese, Armin. Ludwig-Maximilians-University; Alemania
Fil: Kruse, Niels. University Medicine Göttingen; Alemania
Fil: Mollenhauer, Brit. University Medicine Göttingen; Alemania
Fil: Geiss Friedlander, Ruth. University Medicine Göttingen; Alemania
Fil: Ludolph, Albert C.. Ulm University; Alemania
Fil: Freischmidt, Axel. Ulm University; Alemania
Fil: Feiler, Marisa S.. Ulm University; Alemania
Fil: Danzer, Karin M.. Ulm University; Alemania
Fil: Zweckstetter, Markus. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania
Fil: Jovin, Thomas M.. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania
Fil: Simons, Mikael. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania
Fil: Weishaupt, Jochen H.. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania
Fil: Schneider, Anja. Universität Göttingen; Alemania. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania - Materia
-
EXOSOMES
SPREADING
SUMOYLATION
Α-SYNUCLEIN - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/51660
Ver los metadatos del registro completo
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Extracellular vesicle sorting of α-Synuclein is regulated by sumoylationKunadt, MarcelEckermann, KatrinStuendl, AnneGong, JingRusso, BelisaStrauss, KatrinRai, SuryaKügler, SebastianFalomir Lockhart, Lisandro JorgeSchwalbe, MartinKrumova, PetrankaOliveira, Luis M. A.Bähr, MathiasMöbius, WiebkeLevin, JohannesGiese, ArminKruse, NielsMollenhauer, BritGeiss Friedlander, RuthLudolph, Albert C.Freischmidt, AxelFeiler, Marisa S.Danzer, Karin M.Zweckstetter, MarkusJovin, Thomas M.Simons, MikaelWeishaupt, Jochen H.Schneider, AnjaEXOSOMESSPREADINGSUMOYLATIONΑ-SYNUCLEINhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Extracellular 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.Fil: Kunadt, Marcel. Universität Göttingen; Alemania. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania. Max-Planck-Institute for Experimental Medicine; AlemaniaFil: Eckermann, Katrin. Nanoscale Microscopy and Molecular Physiology of the Brain; AlemaniaFil: Stuendl, Anne. Universität Göttingen; AlemaniaFil: Gong, Jing. Max-Planck-Institute for Experimental Medicine; AlemaniaFil: Russo, Belisa. Max-Planck-Institute for Experimental Medicine; AlemaniaFil: Strauss, Katrin. Universität Göttingen; Alemania. Nanoscale Microscopy and Molecular Physiology of the Brain; AlemaniaFil: Rai, Surya. Universität Göttingen; AlemaniaFil: Kügler, Sebastian. Nanoscale Microscopy and Molecular Physiology of the Brain; AlemaniaFil: Falomir Lockhart, Lisandro Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina. Max-Planck-Institute for Biophysical Chemistry; AlemaniaFil: Schwalbe, Martin. Max-Planck-Institute for Biophysical Chemistry; AlemaniaFil: Krumova, Petranka. University Medicine Göttingen; AlemaniaFil: Oliveira, Luis M. A.. Max-Planck-Institute for Biophysical Chemistry; AlemaniaFil: Bähr, Mathias. Nanoscale Microscopy and Molecular Physiology of the Brain; AlemaniaFil: Möbius, Wiebke. Nanoscale Microscopy and Molecular Physiology of the Brain; AlemaniaFil: Levin, Johannes. Ludwig-Maximilians-University; AlemaniaFil: Giese, Armin. Ludwig-Maximilians-University; AlemaniaFil: Kruse, Niels. University Medicine Göttingen; AlemaniaFil: Mollenhauer, Brit. University Medicine Göttingen; AlemaniaFil: Geiss Friedlander, Ruth. University Medicine Göttingen; AlemaniaFil: Ludolph, Albert C.. Ulm University; AlemaniaFil: Freischmidt, Axel. Ulm University; AlemaniaFil: Feiler, Marisa S.. Ulm University; AlemaniaFil: Danzer, Karin M.. Ulm University; AlemaniaFil: Zweckstetter, Markus. Nanoscale Microscopy and Molecular Physiology of the Brain; AlemaniaFil: Jovin, Thomas M.. Nanoscale Microscopy and Molecular Physiology of the Brain; AlemaniaFil: Simons, Mikael. Nanoscale Microscopy and Molecular Physiology of the Brain; AlemaniaFil: Weishaupt, Jochen H.. Nanoscale Microscopy and Molecular Physiology of the Brain; AlemaniaFil: Schneider, Anja. Universität Göttingen; Alemania. Nanoscale Microscopy and Molecular Physiology of the Brain; AlemaniaSpringer2015-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/51660Kunadt, Marcel; Eckermann, Katrin; Stuendl, Anne; Gong, Jing; Russo, Belisa; et al.; Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation; Springer; Acta Neuropathologica; 129; 5; 5-2015; 695-7130001-63221432-0533CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00401-015-1408-1info:eu-repo/semantics/altIdentifier/doi/10.1007/s00401-015-1408-1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:15Zoai:ri.conicet.gov.ar:11336/51660instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:44:15.693CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation |
| title |
Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation |
| spellingShingle |
Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation Kunadt, Marcel EXOSOMES SPREADING SUMOYLATION Α-SYNUCLEIN |
| 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 |
| dc.creator.none.fl_str_mv |
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 |
Kunadt, Marcel |
| 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_role |
author |
| author2 |
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 |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
EXOSOMES SPREADING SUMOYLATION Α-SYNUCLEIN |
| topic |
EXOSOMES SPREADING SUMOYLATION Α-SYNUCLEIN |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| dc.description.none.fl_txt_mv |
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. Fil: Kunadt, Marcel. Universität Göttingen; Alemania. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania. Max-Planck-Institute for Experimental Medicine; Alemania Fil: Eckermann, Katrin. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania Fil: Stuendl, Anne. Universität Göttingen; Alemania Fil: Gong, Jing. Max-Planck-Institute for Experimental Medicine; Alemania Fil: Russo, Belisa. Max-Planck-Institute for Experimental Medicine; Alemania Fil: Strauss, Katrin. Universität Göttingen; Alemania. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania Fil: Rai, Surya. Universität Göttingen; Alemania Fil: Kügler, Sebastian. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania Fil: Falomir Lockhart, Lisandro Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina. Max-Planck-Institute for Biophysical Chemistry; Alemania Fil: Schwalbe, Martin. Max-Planck-Institute for Biophysical Chemistry; Alemania Fil: Krumova, Petranka. University Medicine Göttingen; Alemania Fil: Oliveira, Luis M. A.. Max-Planck-Institute for Biophysical Chemistry; Alemania Fil: Bähr, Mathias. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania Fil: Möbius, Wiebke. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania Fil: Levin, Johannes. Ludwig-Maximilians-University; Alemania Fil: Giese, Armin. Ludwig-Maximilians-University; Alemania Fil: Kruse, Niels. University Medicine Göttingen; Alemania Fil: Mollenhauer, Brit. University Medicine Göttingen; Alemania Fil: Geiss Friedlander, Ruth. University Medicine Göttingen; Alemania Fil: Ludolph, Albert C.. Ulm University; Alemania Fil: Freischmidt, Axel. Ulm University; Alemania Fil: Feiler, Marisa S.. Ulm University; Alemania Fil: Danzer, Karin M.. Ulm University; Alemania Fil: Zweckstetter, Markus. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania Fil: Jovin, Thomas M.. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania Fil: Simons, Mikael. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania Fil: Weishaupt, Jochen H.. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania Fil: Schneider, Anja. Universität Göttingen; Alemania. Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania |
| 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. |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015-05 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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publishedVersion |
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http://hdl.handle.net/11336/51660 Kunadt, Marcel; Eckermann, Katrin; Stuendl, Anne; Gong, Jing; Russo, Belisa; et al.; Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation; Springer; Acta Neuropathologica; 129; 5; 5-2015; 695-713 0001-6322 1432-0533 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/51660 |
| identifier_str_mv |
Kunadt, Marcel; Eckermann, Katrin; Stuendl, Anne; Gong, Jing; Russo, Belisa; et al.; Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation; Springer; Acta Neuropathologica; 129; 5; 5-2015; 695-713 0001-6322 1432-0533 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
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eng |
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openAccess |
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Springer |
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Springer |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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