Affiliations: [a] Department of Neuroscience, University of Tor Vergata, Rome, Italy | [b] Institute of Cellular Biology and Neurobiology, CNR, Rome, Italy
Correspondence:
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Correspondence to: Nadia Canu, MD, PhD. Department of Neuroscience, University of Tor Vergata, Via Montpellier 1, 00133 Rome, Italy and Institute of Cellular Biology and Neurobiology, Consiglio Nazionale delle Ricerche, Via Fosso del Fiorano, 64, 00143 Rome, Italy. Tel.: +39 06 501703233–3245; Fax: +39 06 501703313; E-mail: [email protected]; [email protected].
Abstract: The microtubule associated protein tau plays a crucial role in Alzheimer's disease and in many neurodegenerative disorders collectively known as tauopathies. Recently, tau pathology has been also documented in prion diseases although the possible molecular events linking these two proteins are still unknown. We have investigated the fate of normal cellular prion protein (PrPC) in primary cortical neurons overexpressing tau protein. We found that overexpression of tau reduces PrPC expression at the cell surface and causes its accumulation and aggregation in the cell body but does not affect its maturation and glycosylation. Trapped PrPC forms detergent-insoluble aggregates, mainly composed of un-glycosylated and mono-glycosylated forms of prion protein. Interestingly, co-transfection of tau gene in cortical neurons with a proteasome activity reporter, consisting of a short peptide degron fused to the carboxyl-terminus of green fluorescent protein (GFP-CL1), results in down-regulation of the proteasome system, suggesting a possible mechanism that contributes to intracellular PrPC accumulation. These findings open a new perspective for the possible crosstalk between tau and prion proteins in the pathogenesis of tau induced-neurodegeneration.
