The beta-amyloid precursor protein APP and the microtubule-associated protein Tau play a crucial role in the pathogenesis of Alzheimer's disease (AD). However, the possible molecular events linking these two proteins are still unknown. Here, we show that Fe65, one of the ligands of the APP cytodomain, is associated with Tau in vivo and in vitro, as demonstrated by co-immunoprecipitation, co-localization, and FRET experiments. Deletion studies indicated that the N-terminal domain of Tau and the PTB1 domain of Fe65 are required for this association. This interaction is regulated by the phosphorylation of Tau at selected sites, by glycogen synthase kinase-3beta (GSK3beta) and cyclin-dependent kinase 5 (Cdk5), and requires an intact microtubule network. Furthermore, laser scanner microscopy and co-immunoprecipitation experiments provide preliminary evidence of possible complex(es) involving Tau, Fe65, APP. These findings open new perspectives for the study of the possible crosstalk between these proteins in the pathogenesis of AD. (C) 2004 Elsevier Inc. All rights reserved.

Barbato, C., Canu, N., Zambrano, N., Serafino, A., Minopoli, G., Ciotti, M.t., et al. (2005). Interaction of Tau with Fe65 links tau to APP. NEUROBIOLOGY OF DISEASE, 18(2), 399-408 [10.1016/j.nbd.2004.10.011].

Interaction of Tau with Fe65 links tau to APP

CANU, NADIA
;
CALISSANO, PIETRO
2005-03-01

Abstract

The beta-amyloid precursor protein APP and the microtubule-associated protein Tau play a crucial role in the pathogenesis of Alzheimer's disease (AD). However, the possible molecular events linking these two proteins are still unknown. Here, we show that Fe65, one of the ligands of the APP cytodomain, is associated with Tau in vivo and in vitro, as demonstrated by co-immunoprecipitation, co-localization, and FRET experiments. Deletion studies indicated that the N-terminal domain of Tau and the PTB1 domain of Fe65 are required for this association. This interaction is regulated by the phosphorylation of Tau at selected sites, by glycogen synthase kinase-3beta (GSK3beta) and cyclin-dependent kinase 5 (Cdk5), and requires an intact microtubule network. Furthermore, laser scanner microscopy and co-immunoprecipitation experiments provide preliminary evidence of possible complex(es) involving Tau, Fe65, APP. These findings open new perspectives for the study of the possible crosstalk between these proteins in the pathogenesis of AD. (C) 2004 Elsevier Inc. All rights reserved.
mar-2005
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/09 - FISIOLOGIA
English
Con Impact Factor ISI
Alzheimer's disease; APP; Cerebellar granule neurons; Fe65; Tau; Tau phosphorylation
amyloid beta protein; glycogen synthase kinase; glycogen synthase kinase 3beta; tau protein; Alzheimer disease; amino terminal sequence; animal cell; animal tissue; article; cellular distribution; controlled study; gene deletion; immunoprecipitation; ligand binding; molecular dynamics; nonhuman; pathogenesis; priority journal; protein interaction; rat; Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Animals, Newborn; Brain; Cells, Cultured; Cyclin-Dependent Kinase 5; Cyclin-Dependent Kinases; Disease Models, Animal; Dogs; Fluorescence Resonance Energy Transfer; Fluorescent Antibody Technique; Gene Transfer Techniques; Glycogen Synthase Kinase 3; Microscopy, Confocal; Microtubules; Nerve Tissue Proteins; Neurons; Nuclear Proteins; Phosphorylation; Protein Structure, Tertiary; Rats; Rats, Wistar; tau Proteins
Barbato, C., Canu, N., Zambrano, N., Serafino, A., Minopoli, G., Ciotti, M.t., et al. (2005). Interaction of Tau with Fe65 links tau to APP. NEUROBIOLOGY OF DISEASE, 18(2), 399-408 [10.1016/j.nbd.2004.10.011].
Barbato, C; Canu, N; Zambrano, N; Serafino, A; Minopoli, G; Ciotti, Mt; Amadoro, G; Russo, T; Calissano, P
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/56982
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