Overexpression of Tau protein in neuronal and non-neuronal cells produces alterations in the organization of intracellular membranous components and tubulin cytoskeleton

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Abnormal intracellular aggregation of Tau protein is a pathological condition leading to neuronal death in Alzheimer´s disease (AD) and several Tauopathies. It has been proposed that oligomers and non-fibrillar aggregates of Tau protein may produce alterations in the morphology and normal functioning of neurons previous the formation of insoluble filaments. Nevertheless, the mechanism by which Tau produces these alterations is still under investigation. In this study we evaluated the possible mechanism by which the overabundance of full-length Tau and several truncated variants alter the organization of distinct membranous organelles including nuclei, Golgi apparatus and plasma membrane in cultured neuronal and non-neuronal cells. We transiently transfected undifferentiated neuronal and glial cell lines with plasmids encoding the sequence of full-length Tau (hTau40), and distinct N- and C- termini truncated Tau variants. After 48 hours of transfection cells were processed for multilabeling immunofluorescence and analyzed by confocal microscopy. In cells expressing Tau we found extensive lobulation of the nuclei, fragmentation of the Golgi apparatus, and plasma membrane blebbing. These alterations were closely associated with Tau-induced ring-shaped microtubule bundles. These structures were highly resistant and were induced by either truncated or non-truncated Tau proteins. We proposed a new mechanisms of Tau toxicity implying structural changes in the subcellular organization of membranous compartments, all promoted by a mechanical force generated by Tau-induced ring-shaped microtubule bundles