The FK506-binding protein FKBP52 in vitro ...
Type de document :
Article dans une revue scientifique
DOI :
URL permanente :
Titre :
The FK506-binding protein FKBP52 in vitro induces aggregation of truncated Tau forms with prion-like behavior
Auteur(s) :
Giustiniani, Julien [Auteur]
Maladies et hormones du système nerveux [DHNS]
Guillemeau, Kevin [Auteur]
Maladies et hormones du système nerveux [DHNS]
Dounane, Omar [Auteur]
Maladies et hormones du système nerveux [DHNS]
Sardin, Elodie [Auteur]
Maladies et hormones du système nerveux [DHNS]
Huvent, Isabelle [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Schmitt, Alain [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Hamdane, Malika [Auteur]
Buee, Luc [Auteur]
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]
Maladies et hormones du système nerveux [DHNS]
Chambraud, Béatrice [Auteur]
Maladies et hormones du système nerveux [DHNS]
Maladies et hormones du système nerveux [DHNS]
Guillemeau, Kevin [Auteur]
Maladies et hormones du système nerveux [DHNS]
Dounane, Omar [Auteur]
Maladies et hormones du système nerveux [DHNS]
Sardin, Elodie [Auteur]
Maladies et hormones du système nerveux [DHNS]
Huvent, Isabelle [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Schmitt, Alain [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Hamdane, Malika [Auteur]
Buee, Luc [Auteur]
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]
Maladies et hormones du système nerveux [DHNS]
Chambraud, Béatrice [Auteur]
Maladies et hormones du système nerveux [DHNS]
Titre de la revue :
The FASEB Journal
Numéro :
29
Pagination :
3171-3181
Date de publication :
2015-08
ISSN :
0892-6638, 1530-6860
Mot(s)-clé(s) en anglais :
Microtubule
Immunophilin
Tau assembly
Seeding
Immunophilin
Tau assembly
Seeding
Discipline(s) HAL :
Chimie/Chimie théorique et/ou physique
Résumé en anglais : [en]
Tauopathies, including Alzheimer's disease (AD), are neurodegenerative diseases associated with the pathologic aggregation of human brain Tau protein. Neuronal Tau is involved in microtubule (MT) formation and stabilization. ...
Lire la suite >Tauopathies, including Alzheimer's disease (AD), are neurodegenerative diseases associated with the pathologic aggregation of human brain Tau protein. Neuronal Tau is involved in microtubule (MT) formation and stabilization. We showed previously that the immunophilin FK506‐binding protein of MW ~52 kDa (FKBP52) interferes with this function of full‐length Tau and provokes aggregation of a disease‐related mutant of Tau. To dissect the molecular interaction between recombinant human FKBP52 and Tau, here, we study the effect of FKBP52 on a functional Tau fragment (Tau‐F4, Ser208‐Ser324) containing part of the proline‐rich region and MT‐binding repeats. Therefore, we perform MT assembly and light‐scattering assays, blue native PAGE analysis, electron microscopy, and Tau seeding experiments in SH‐SY5Y human neuroblastoma cells. We show that FKBP52 (6 μM) prevents MT formation generated by Tau‐F4 (5 μM) and induces Tau‐F4 oligomerization and aggregation. Electron microscopy analyses show granular oligomers and filaments of Tau‐F4 after short‐time FKBP52 incubation. We demonstrate that the terminal parts of Tau interfere with the effects of FKBP52. Finally, we find that FKBP52‐induced Tau‐F4 oligomers cannot only generate in vitro, direct conformational changes in full‐length Tau and that their uptake into neuronal cells can equally lead to aggregation of wild‐type endogenous Tau. This suggests a potential prion‐like properly of these particular Tau‐F4 aggregates. Collectively, our results strengthen the hypothesis of FKBP52 involvement in the Tau pathogenicity process.Lire moins >
Lire la suite >Tauopathies, including Alzheimer's disease (AD), are neurodegenerative diseases associated with the pathologic aggregation of human brain Tau protein. Neuronal Tau is involved in microtubule (MT) formation and stabilization. We showed previously that the immunophilin FK506‐binding protein of MW ~52 kDa (FKBP52) interferes with this function of full‐length Tau and provokes aggregation of a disease‐related mutant of Tau. To dissect the molecular interaction between recombinant human FKBP52 and Tau, here, we study the effect of FKBP52 on a functional Tau fragment (Tau‐F4, Ser208‐Ser324) containing part of the proline‐rich region and MT‐binding repeats. Therefore, we perform MT assembly and light‐scattering assays, blue native PAGE analysis, electron microscopy, and Tau seeding experiments in SH‐SY5Y human neuroblastoma cells. We show that FKBP52 (6 μM) prevents MT formation generated by Tau‐F4 (5 μM) and induces Tau‐F4 oligomerization and aggregation. Electron microscopy analyses show granular oligomers and filaments of Tau‐F4 after short‐time FKBP52 incubation. We demonstrate that the terminal parts of Tau interfere with the effects of FKBP52. Finally, we find that FKBP52‐induced Tau‐F4 oligomers cannot only generate in vitro, direct conformational changes in full‐length Tau and that their uptake into neuronal cells can equally lead to aggregation of wild‐type endogenous Tau. This suggests a potential prion‐like properly of these particular Tau‐F4 aggregates. Collectively, our results strengthen the hypothesis of FKBP52 involvement in the Tau pathogenicity process.Lire moins >
Langue :
Anglais
Audience :
Non spécifiée
Projet ANR :
Établissement(s) :
CHU Lille
CNRS
Inserm
Université de Lille
CNRS
Inserm
Université de Lille
Collections :
Équipe(s) de recherche :
RMN et interactions moléculaires
Date de dépôt :
2020-02-12T15:44:56Z
2021-04-28T08:57:22Z
2021-04-28T08:57:22Z