Tau inhibits tubulin oligomerization induced by prion protein |
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Authors: | Katarzyna M. OsieckaHanna Nieznanska Krzysztof J. SkowronekJolanta Jozwiak Krzysztof Nieznanski |
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Affiliation: | Department of Biochemistry, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093 Warsaw, Poland |
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Abstract: | In previous studies we have demonstrated that prion protein (PrP) interacts with tubulin and disrupts microtubular cytoskeleton by inducing tubulin oligomerization. These observations may explain the molecular mechanism of toxicity of cytoplasmic PrP in transmissible spongiform encephalopathies (TSEs). Here, we check whether microtubule associated proteins (MAPs) that regulate microtubule stability, influence the PrP-induced oligomerization of tubulin. We show that tubulin preparations depleted of MAPs are more prone to oligomerization by PrP than those containing traces of MAPs. Tau protein, a major neuronal member of the MAPs family, reduces the effect of PrP. Importantly, phosphorylation of Tau abolishes its ability to affect the PrP-induced oligomerization of tubulin. We propose that the binding of Tau stabilizes tubulin in a conformation less susceptible to oligomerization by PrP. Since elevated phosphorylation of Tau leading to a loss of its function is observed in Alzheimer disease and related tauopathies, our results point at a possible molecular link between these neurodegenerative disorders and TSEs. |
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Keywords: | AD, Alzheimer disease CBB, Coomassie brilliant blue CtmPrP, transmembrane form of prion protein with the C-terminus residing in the lumen of endoplasmic reticulum cytoPrP, cytosolic prion protein EDC, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide ER, endoplasmic reticulum GPI, glycosylphosphatidylinositol GSK3, glycogen synthase kinase 3 mAb, monoclonal antibody MAPs, microtubule-associated proteins pep1-30, peptide corresponding to PrP sequence 1-30 PKA, protein kinase A PMDs, protein misfolding diseases PrP, prion protein PrPC, cellular form of prion protein PrPSc, TSE (scrapie) form of prion protein rTau, recombinant Tau SNHS, N-hydroxysulfosuccinimide TSEs, transmissible spongiform encephalopathies |
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