Francelle, Laetitia

[["dc.bibliographiccitation.firstpage","76"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","85"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Blum, David"],["dc.contributor.author","Herrera, Federico"],["dc.contributor.author","Francelle, Laetitia"],["dc.contributor.author","Mendes, Tiago"],["dc.contributor.author","Basquin, Marie"],["dc.contributor.author","Obriot, Helene"],["dc.contributor.author","Demeyer, Dominique"],["dc.contributor.author","Sergeant, Nicolas"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Brouillet, Emmanuel"],["dc.contributor.author","Buée, Luc"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2018-11-07T10:03:30Z"],["dc.date.available","2018-11-07T10:03:30Z"],["dc.date.issued","2015"],["dc.description.abstract","Tau abnormalities play a central role in several neurodegenerative diseases, collectively known as tauopathies. In the present study, we examined whether mutant huntingtin (mHtt), which causes Huntington's disease (HD), modifies Tau phosphorylation and subcellular localization using cell and mouse HD models. Initially, we used novel bimolecular fluorescence complementation assays in live cells to evaluate Tau interactions with either wild type (25QHtt) ormutant huntingtin(103QHtt). While 25QHtt and Tau interacted at the level of the microtubule network, 103QHtt and Tau interacted and formed 'ring-like' inclusions localized in the vicinity of the microtubular organizing center (MTOC). Fluorescence recovery after photobleaching experiments also indicated that, whereas homomeric 103QHtt/103QHtt pairs rapidly re-entered into inclusions, heteromeric 103QHtt/Tau pairs remained excluded from the 'ring-like' inclusions. Interestingly, in vitro Tau relocalization was associated to Tau hyperphosphorylation. Consistent with this observation, we found strong Tau hyperphosphorylation in brain samples from two different mouse models of HD, R6/2 and 140CAG knock-in. This was associated with a significant reduction in the levels of Tau phosphatases (PP1, PP2A and PP2B), with no apparent involvement of major Tau kinases. Thus, the present study strongly suggests that expression of mHtt leads to Tau hyperphosphorylation, relocalization and sequestration through direct protein-protein interactions in inclusion-like compartments in the vicinity of the MTOC. Likewise, our data also suggest that Tau alterations may also contribute to HD pathogenesis."],["dc.identifier.doi","10.1093/hmg/ddu421"],["dc.identifier.isi","000350135400007"],["dc.identifier.pmid","25143394"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38481"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1460-2083"],["dc.relation.issn","0964-6906"],["dc.title","Mutant huntingtin alters Tau phosphorylation and subcellular distribution"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e2000374"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","PLoS Biology"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","de Oliveira, Rita Machado"],["dc.contributor.author","Miranda, Hugo Vicente"],["dc.contributor.author","Francelle, Laetitia"],["dc.contributor.author","Pinho, Raquel"],["dc.contributor.author","Szegoe, Eva Monika"],["dc.contributor.author","Martinho, Renato"],["dc.contributor.author","Munari, Francesca"],["dc.contributor.author","Lazaro, Diana F."],["dc.contributor.author","Moniot, Sebastien"],["dc.contributor.author","Guerreiro, Patricia S."],["dc.contributor.author","Fonseca, Luis"],["dc.contributor.author","Marijanovic, Zrinka"],["dc.contributor.author","Antas, Pedro"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Enguita, Francisco Javier"],["dc.contributor.author","Fauvet, Bruno"],["dc.contributor.author","Penque, Deborah"],["dc.contributor.author","Pais, Teresa Faria"],["dc.contributor.author","Tong, Qiang"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Kuegler, Sebastian"],["dc.contributor.author","Lashuel, Hilal Ahmed"],["dc.contributor.author","Steegborn, Clemens"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2018-11-07T10:26:48Z"],["dc.date.available","2018-11-07T10:26:48Z"],["dc.date.issued","2017"],["dc.description.abstract","Sirtuin genes have been associated with aging and are known to affect multiple cellular pathways. Sirtuin 2 was previously shown to modulate proteotoxicity associated with ageassociated neurodegenerative disorders such as Alzheimer and Parkinson disease (PD). However, the precise molecular mechanisms involved remain unclear. Here, we provide mechanistic insight into the interplay between sirtuin 2 and alpha-synuclein, the major component of the pathognomonic protein inclusions in PD and other synucleinopathies. We found that alpha-synuclein is acetylated on lysines 6 and 10 and that these residues are deacetylated by sirtuin 2. Genetic manipulation of sirtuin 2 levels in vitro and in vivo modulates the levels of alpha-synuclein acetylation, its aggregation, and autophagy. Strikingly, mutants blocking acetylation exacerbate alpha-synuclein toxicity in vivo, in the substantia nigra of rats. Our study identifies alpha-synuclein acetylation as a key regulatory mechanism governing alpha-synuclein aggregation and toxicity, demonstrating the potential therapeutic value of sirtuin 2 inhibition in synucleinopathies."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1371/journal.pbio.2000374"],["dc.identifier.isi","000397909600002"],["dc.identifier.pmid","28257421"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14377"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43121"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Public Library Science"],["dc.relation.haserratum","/handle/2/102935"],["dc.relation.issn","1545-7885"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The mechanism of sirtuin 2-mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]