Immunophilin FKBP52 induces Tau-P301L ...
Type de document :
Article dans une revue scientifique
DOI :
URL permanente :
Titre :
Immunophilin FKBP52 induces Tau-P301L filamentous assembly in vitro and modulates its activity in a model of tauopathy
Auteur(s) :
Giustiniani, Julien [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Chambraud, Béatrice [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Sardin, Elodie [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Dounane, Omar [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Guillemeau, Kevin [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Nakatani, Hiroko [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Paquet, Dominik [Auteur]
German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen [DZNE]
Kamah, Amina [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Landrieu, Isabelle [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Lippens, Guy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Baulieu, Etienne-Emile [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Tawk, Marcel [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Chambraud, Béatrice [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Sardin, Elodie [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Dounane, Omar [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Guillemeau, Kevin [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Nakatani, Hiroko [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Paquet, Dominik [Auteur]
German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen [DZNE]
Kamah, Amina [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Landrieu, Isabelle [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Lippens, Guy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Baulieu, Etienne-Emile [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Tawk, Marcel [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Titre de la revue :
Proceedings of the National Academy of Sciences
Numéro :
111
Pagination :
4584-4589
Date de publication :
2014-03-25
ISSN :
0027-8424, 1091-6490
Mot(s)-clé(s) en anglais :
FKBP
Tau assembly
Tau-P301L dementia
Tau assembly
Tau-P301L dementia
Discipline(s) HAL :
Chimie/Chimie théorique et/ou physique
Résumé en anglais : [en]
The Tau protein is the major component of intracellular filaments observed in a number of neurodegenerative diseases known as tauopathies. The pathological mutant of Tau containing a proline-to-leucine mutation at position ...
Lire la suite >The Tau protein is the major component of intracellular filaments observed in a number of neurodegenerative diseases known as tauopathies. The pathological mutant of Tau containing a proline-to-leucine mutation at position 301 (P301L) leads to severe human tauopathy. Here, we assess the impact of FK506-binding protein with a molecular mass of ∼52 kDa (FKBP52), an immunophilin protein that interacts with physiological Tau, on Tau-P301L activity. We identify a direct interaction of FKBP52 with Tau-P301L and its phosphorylated forms and demonstrate FKBP52's ability to induce the formation of Tau-P301L oligomers. EM analysis shows that Tau-P301L oligomers, induced by FKBP52, can assemble into filaments. In the transgenic zebrafish expressing the human Tau-P301L mutant, FKBP52 knockdown is sufficient to redrive defective axonal outgrowth and branching related to Tau-P301L expression in spinal primary motoneurons. This result correlates with a significant reduction of pT181 pathological phosphorylated Tau and with recovery of the stereotypic escape response behavior. Collectively, FKBP52 appears to be an endogenous candidate that directly interacts with the pathogenic Tau-P301L and modulates its function in vitro and in vivo.Lire moins >
Lire la suite >The Tau protein is the major component of intracellular filaments observed in a number of neurodegenerative diseases known as tauopathies. The pathological mutant of Tau containing a proline-to-leucine mutation at position 301 (P301L) leads to severe human tauopathy. Here, we assess the impact of FK506-binding protein with a molecular mass of ∼52 kDa (FKBP52), an immunophilin protein that interacts with physiological Tau, on Tau-P301L activity. We identify a direct interaction of FKBP52 with Tau-P301L and its phosphorylated forms and demonstrate FKBP52's ability to induce the formation of Tau-P301L oligomers. EM analysis shows that Tau-P301L oligomers, induced by FKBP52, can assemble into filaments. In the transgenic zebrafish expressing the human Tau-P301L mutant, FKBP52 knockdown is sufficient to redrive defective axonal outgrowth and branching related to Tau-P301L expression in spinal primary motoneurons. This result correlates with a significant reduction of pT181 pathological phosphorylated Tau and with recovery of the stereotypic escape response behavior. Collectively, FKBP52 appears to be an endogenous candidate that directly interacts with the pathogenic Tau-P301L and modulates its function in vitro and in vivo.Lire moins >
Langue :
Anglais
Audience :
Non spécifiée
Établissement(s) :
CNRS
Université de Lille
Université de Lille
Équipe(s) de recherche :
RMN et interactions moléculaires
Date de dépôt :
2020-02-12T15:44:59Z
2021-03-05T14:21:08Z
2021-03-05T14:21:08Z