title: Altered intracellular distribution of PrPC and impairment of proteasome activity in tau overexpressing cortical neurons.
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 (PrP(C)) in primary cortical neurons overexpressing tau protein. We found that overexpression of tau reduces PrP(C) expression at the cell surface and causes its accumulation and aggregation in the cell body but does not affect its maturation and glycosylation. Trapped PrP(C) 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 PrP(C) accumulation. These findings open a new perspective for the possible crosstalk between tau and prion proteins in the pathogenesis of tau induced-neurodegeneration.
authors.affiliation: Department of Neuroscience, University of Tor Vergata, Rome, Italy. n.canu@inmm.cnr.it
authors.forename: Nadia
authors.initials: N
authors.lastname: Canu
authors.forename: Ilaria
authors.initials: I
authors.lastname: Filesi
authors.forename: Andrea
authors.initials: A
authors.lastname: Pristerà
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ciotti
authors.forename: Silvia
authors.initials: S
authors.lastname: Biocca
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D007424:Intracellular Fluid / Q000201:enzymology / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D018621:PrPC Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics*; D011247:Pregnancy; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011485:Protein Binding / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D016875:tau Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018621:PrPC Proteins; D061988:Proteasome Inhibitors; D016875:tau Proteins; D046988:Proteasome Endopeptidase Complex