Abstract
Pathologically aggregated and hyperphosphorylated tau protein is a characteristic feature of Alzheimer’s disease and related tauopathies. The best known physiological function of tau is the stabilization of neuronal microtubules, which can be regulated by phosphorylation. However, other functions have recently begun to emerge. Here we focus on two new aspects, the role of tau phosphorylation in the outgrowth of cell processes, and the role of tau in intracellular traffic. 1) Phosphorylation of tau at Ser/Thr-Pro motifs is somewhat inhibitory to process outgrowth in Sf9 cells, but (transient) phosphorylation at KXGS motifs in the repeat domain is essential for process formation, even though this type of phosphorylation destabilizes microtubules. 2) Elevation of tau inhibits intracellular transport of vesicles and cell organelles, preferentially in the kinesin-dependent direction towards the cell periphery. This leads to an accumulation of mitochondria or intermediate filaments in the cell center and their depletion from neuntes, thus making neurites vulnerable. This process would explain a toxic role of elevated tau in Alzheimer’s disease.
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Mandelkow, EM. et al. (2000). Tau Protein: Role in Intracellular Traffic and Development of Cell Polarity. In: Lee, V.MY., Trojanowski, J.Q., Buée, L., Christen, Y. (eds) Fatal Attractions: Protein Aggregates in Neurodegenerative Disorders. Research and Perspectives in Alzheimer’s Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-04056-0_9
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DOI: https://doi.org/10.1007/978-3-662-04056-0_9
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