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dc.contributor.author
Yin, Guowei
dc.contributor.author
Lopes da Fonseca, Tomas
dc.contributor.author
Eisbach, Sibylle E.
dc.contributor.author
Anduaga, Ane Martin
dc.contributor.author
Breda, Carlo
dc.contributor.author
Orcellet, Maria Laura
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dc.contributor.author
Szegő, Eva M.
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Guerreiro, Patria
dc.contributor.author
Lázaro, Diana F.
dc.contributor.author
Braus, Gerhard H.
dc.contributor.author
Fernandez, Claudio Oscar
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dc.contributor.author
Griesinger, Christian
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Becker, Stefan
dc.contributor.author
Goody, Roger S.
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Itzen, Aymelt
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Giorgini, Flaviano
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Outeiro, Tiago F.
dc.contributor.author
Zweckstetter, Markus
dc.date.available
2017-12-01T13:45:55Z
dc.date.issued
2014-06
dc.identifier.citation
Yin, Guowei; Lopes da Fonseca, Tomas; Eisbach, Sibylle E.; Anduaga, Ane Martin; Breda, Carlo; et al.; α-Synuclein interacts with the switch region of Rab8a in a Ser129 phosphorylation-dependent manner; Academic Press Inc Elsevier Science; Neurobiology Of Disease; 70; 6-2014; 149-161
dc.identifier.issn
1095-953X
dc.identifier.uri
http://hdl.handle.net/11336/29424
dc.description.abstract
Alpha-synuclein (αS) misfolding is associated with Parkinson's disease (PD) but little is known about the mechanisms underlying αS toxicity. Increasing evidence suggests that defects in membrane transport play an important role in neuronal dysfunction. Here we demonstrate that the GTPase Rab8a interacts with αS in rodent brain. NMR spectroscopy reveals that the C-terminus of αS binds to the functionally important switch region as well as the C-terminal tail of Rab8a. In line with a direct Rab8a/αS interaction, Rab8a enhanced αS aggregation and reduced αS-induced cellular toxicity. In addition, Rab8 – the Drosophila ortholog of Rab8a – ameliorated αS-oligomer specific locomotor impairment and neuron loss in fruit flies. In support of the pathogenic relevance of the αS–Rab8a interaction, phosphorylation of αS at S129 enhanced binding to Rab8a, increased formation of insoluble αS aggregates and reduced cellular toxicity. Our study provides novel mechanistic insights into the interplay of the GTPase Rab8a and αS cytotoxicity, and underscores the therapeutic potential of targeting this interaction.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Academic Press Inc Elsevier Science
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Α-Synuclein
dc.subject
Aggregation
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Parkinson'S Disease
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Phosphorylation
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Rab Gtpase
dc.subject.classification
Otras Ciencias Biológicas
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
α-Synuclein interacts with the switch region of Rab8a in a Ser129 phosphorylation-dependent manner
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-11-24T19:36:29Z
dc.identifier.eissn
0969-9961
dc.journal.volume
70
dc.journal.pagination
149-161
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
Oxford
dc.description.fil
Fil: Yin, Guowei. Max Planck Institute Of Biochemistry.; Alemania
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Fil: Lopes da Fonseca, Tomas. Universität Göttingen; Alemania. Research Center Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania
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Fil: Eisbach, Sibylle E.. Universität Göttingen; Alemania. Research Center Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania
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Fil: Anduaga, Ane Martin. University of Leicester; Reino Unido
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Fil: Breda, Carlo. University of Leicester; Reino Unido
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Fil: Orcellet, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
dc.description.fil
Fil: Szegő, Eva M.. Universität Göttingen; Alemania. Research Center Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania
dc.description.fil
Fil: Guerreiro, Patria. Universität Göttingen; Alemania. Research Center Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania
dc.description.fil
Fil: Lázaro, Diana F.. Universität Göttingen; Alemania. Research Center Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania
dc.description.fil
Fil: Braus, Gerhard H.. Universität Göttingen; Alemania. Research Center Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania
dc.description.fil
Fil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
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Fil: Griesinger, Christian. Max Planck Institute for Biophysical Chemistry; Alemania
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Fil: Becker, Stefan. Max Planck Institute for Biophysical Chemistry; Alemania
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Fil: Goody, Roger S.. Max-Planck-Institute of Molecular Physiology; Alemania
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Fil: Itzen, Aymelt. Universitat Technical Zu Munich; Alemania. Max-Planck-Institute of Molecular Physiology; Alemania
dc.description.fil
Fil: Giorgini, Flaviano. University of Leicester; Reino Unido
dc.description.fil
Fil: Outeiro, Tiago F.. Universität Göttingen; Alemania. Research Center Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania
dc.description.fil
Fil: Zweckstetter, Markus. Max Planck Institute for Biophysical Chemistry; Alemania. German Center for Neurodegenerative Diseases; Alemania. Research Center Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania
dc.journal.title
Neurobiology Of Disease
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S096999611400182X
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.nbd.2014.06.018
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