title: Tau inhibits tubulin oligomerization induced by prion protein.
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.
authors.affiliation: Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: Katarzyna M
authors.initials: KM
authors.lastname: Osiecka
authors.forename: Hanna
authors.initials: H
authors.lastname: Nieznanska
authors.forename: Krzysztof J
authors.initials: KJ
authors.lastname: Skowronek
authors.forename: Jolanta
authors.initials: J
authors.lastname: Jozwiak
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Nieznanski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008954:Models, Biological; D011328:Prions / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects*; D055550:Protein Stability / Q000187:drug effects; D013552:Swine; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D016875:tau Proteins / Q000494:pharmacology* / Q000502:physiology
chemical_list: C054369:MAPT protein, human; D008869:Microtubule-Associated Proteins; D011328:Prions; D014404:Tubulin; D050257:Tubulin Modulators; D016875:tau Proteins