Binding of Hsp90 to Tau Promotes a Conformational Change and Aggregation of Tau Protein

Article type: Research Article

Authors: Tortosa, Elena^a | Santa-Maria, Ismael^{a; b} | Moreno, Francisco^a | Lim, Filip^a | Perez, Mar^{a; c} | Avila, Jesús^{a; b; *}

Affiliations: [a] Centro de Biología Molecular “Severo Ochoa” CSIC/UAM, Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain | [b] CIBERNED, Spain | [c] Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain

Correspondence: [*] Corresponding author: Jesús Avila, Centro de Biología Molecular “Severo Ochoa”, Calle Nicolás Cabrera 1, Campus de Cantoblanco, Universidad Autónoma de Madrid, 28049 Madrid, Spain. Tel.: +34 911964592; Fax: +34 911964420; E-mail: [email protected].

Abstract: Tau pathology, associated with Alzheimer's disease, is characterized by the presence of phosphorylated and aggregated tau. Phosphorylation of tau takes place mainly in the vicinity of the tubulin-binding region of the molecule and its self aggregation is also mediated via this tubulin-binding region. Tau phosphorylation and aggregation have been related with conformational changes of the protein. These changes could be regulated by chaperones such as heat shock proteins, since one of these, heat shock protein 90 (Hsp90), has already been described as a putative tau-binding protein. In this work, we have confirmed the interaction of Hsp90 with tau protein and report that binding of Hsp90 to tau facilitates a conformational change that could result in its phosphorylation by glycogen synthase kinase 3 and its aggregation into filamentous structures.

Keywords: Aggregation, Hsp90, phosphorylation, tau

DOI: 10.3233/JAD-2009-1049

Journal: Journal of Alzheimer's Disease, vol. 17, no. 2, pp. 319-325, 2009