Title :

Immunophilin FKBP52 induces Tau-P301L filamentous assembly in vitro and modulates its activity in a model of tauopathy

Author(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]

Journal title :

Proceedings of the National Academy of Sciences

Volume number :

111

Pages :

4584-4589

Publication date :

2014-03-25

ISSN :

0027-8424, 1091-6490

English keyword(s) :

FKBP
Tau assembly
Tau-P301L dementia

HAL domain(s) :

Chimie/Chimie théorique et/ou physique

English abstract : [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 ...
Show more >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.Show less >

Language :

Anglais

Audience :

Non spécifiée

Administrative institution(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

RMN et interactions moléculaires

Submission date :

2020-02-12T15:44:59Z
2021-03-05T14:21:08Z