role for FKBP52 in Tau protein function

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 6; pp. 2658 - 2663
• Main Authors: Chambraud, Béatrice, Sardin, Elodie, Giustiniani, Julien, Dounane, Omar, Schumacher, Michael, Goedert, Michel, Baulieu, Etienne-Emile
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 09-02-2010; National Acad Sciences
• Subjects: Alzheimers disease; Animals; Antibodies; Binding sites; Biochemistry; Biological Sciences; Blotting, Western; Brain; Brain - metabolism; Cells; Chromosomes; Dementia; Doxycycline - pharmacology; Gene expression; Humans; Male; Microtubules; Microtubules - metabolism; Nerve Growth Factor - pharmacology; Nervous system; Neurites; Neurites - drug effects; Neurites - physiology; Neurons; PC12 Cells; Phosphorylation; Protein isoforms; Proteins; Rats; Rats, Sprague-Dawley; Tacrolimus Binding Proteins - genetics; Tacrolimus Binding Proteins - metabolism; Tacrolimus Binding Proteins - physiology; Tau proteins; tau Proteins - genetics; tau Proteins - metabolism; tau Proteins - physiology; Transfection
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0914957107

Tau is a microtubule-associated protein, which is widely expressed in the central nervous system, predominantly in neurons, where it regulates microtubule dynamics, axonal transport, and neurite outgrowth. The aberrant assembly of Tau is the hallmark of several human neurodegenerative diseases, collectively known as tauopathies. They include Alzheimer's disease, Pick's disease, progressive supranuclear palsy, and frontotemporal dementia and parkinsonism linked to chromosome 17. Several abnormalities in Tau, such as hyperphosphorylation and aggregation, alter its function and are central to the pathogenic process. Here, we describe biochemical and functional interactions between FKBP52 and Tau. FKBP52 is a member of the FKBP (FK506-binding protein) family that comprises intracellular protein effectors of immunosuppressive drugs (such as FK506 and rapamycin). We found that FKBP52, which is abundant in brain, binds directly and specifically to Tau, especially in its hyperphosphorylated form. The relevance of this observation was confirmed by the colocalization of both proteins in the distal part of the axons of cortical neurons and by the antagonistic effect of FKBP52 on the ability of Tau to promote microtubule assembly. Overexpression of FKBP52 in differentiated PC12 cells prevented the accumulation of Tau and resulted in reduced neurite length. Taken together, these findings indicate a role for FKBP52 in Tau function and may help to decipher and modulate the events involved in Tau-induced neurodegeneration.