Tau inhibits tubulin oligomerization induced by prion protein

• Published in: Biochimica et biophysica acta Vol. 1813; no. 10; pp. 1845 - 1853
• Main Authors: Osiecka, Katarzyna M., Nieznanska, Hanna, Skowronek, Krzysztof J., Jozwiak, Jolanta, Nieznanski, Krzysztof
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-10-2011
• Subjects: Alzheimer disease; Amino Acid Sequence; Animals; Cells, Cultured; Down-Regulation - drug effects; Humans; Microtubule-Associated Proteins - metabolism; Models, Biological; Phosphorylation; Prion disease; Prion protein; Prions - pharmacology; Protein Binding - drug effects; Protein Multimerization - drug effects; Protein Stability - drug effects; Swine; Tau; tau Proteins - pharmacology; tau Proteins - physiology; Tubulin; Tubulin - metabolism; Tubulin Modulators - pharmacology; Up-Regulation - drug effects; pep1-30; SNHS; GPI; CBB; PrPSc; Phosphorylation; cytoPrP; EDC; Alzheimer disease; PMDs; Tau; Tubulin; MAPs; GSK3; CtmPrP; Prion protein; Prion disease; AD; rTau; PKA; TSEs; ER; mAb; PrP; PrPC
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2011.06.016

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.
► Tau inhibits PrP-induced oligomerization of tubulin. ► Tau does not compete with PrP for binding site on tubulin. ► Tau stabilizes tubulin in a form less susceptible to PrP-induced oligomerization. ► Phosphorylation regulates Tau's ability to inhibit PrP-induced oligomerization. ► Tau phosphorylation may indirectly enhance neurotoxicity of cytosolic PrP.