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Phosphorylation of Tau and Its Relationship with Alzheimer Paired Helical Filaments

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Alzheimer’s Disease: Lessons from Cell Biology

Part of the book series: Research and Perspectives in Alzheimer’s Disease ((ALZHEIMER))

Summary

This paper summarizes our recent studies on microtubule-associated protein tau and its pathological state resembling that of the paired helical filaments of Alzheimer’s disease. The Alzheimer-like state of tau protein can be identified and analyzed in terms of certain phosphorylation sites and phosphorylation-dependent antibody epitopes. It can be induced by protein kinases which tend to phosphorylate serine or threonine residues followed by a proline; these include mitogen-activated protein kinase (MAPK), glycogen-synthase kinase-3 (GSK-3), or cyclin-dependent kinase-5 (cdk5). These kinases are tightly associated with microtubules as well as with paired helical filaments. In addition, the phosphorylation of serine 262 has a pronounced influence on the binding of tau to microtubules. All of the phosphorylation sites can be cleared by the phosphatases calcineurin and PP-2A, but not by PP-1. Structurally, tau appears as a rod-like molecule. It tends to self-associate into dimers whose monomers are antiparallel. Constructs of truncated tau made up of the microtubule binding domain can be assembled into paired helical filaments in vitro.

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Authors and Affiliations

  1. Max-Planck-Unit for Structural Molecular Biology, c/o DESY, Notkestrasse 85, 22603, Hamburg, Germany

    E.-M. Mandelkow

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  1. E.-M. Mandelkow
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  2. J. Biernat
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  3. B. Lichtenberg-Kraag
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  4. G. Drewes
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  5. H. Wille
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  6. N. Gustke
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  7. K. Baumann
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  8. E. Mandelkow
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Editors and Affiliations

  1. Harvard Medical School, Brigham and Women’s Hospital, 221 Longwood Avenue, 02115, Boston, MA, USA

    K. S. Kosik M.D. (Associate Professor of Neurology and Neuroscience) & D. J. Selkoe M.D. (Professor of Neurology and Neuroscience) (Associate Professor of Neurology and Neuroscience) &  (Professor of Neurology and Neuroscience)

  2. Fondation IPSEN, 24, rue Erlanger, 75781, Paris, France

    Y. Christen Ph.D.

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Mandelkow, EM. et al. (1995). Phosphorylation of Tau and Its Relationship with Alzheimer Paired Helical Filaments. In: Kosik, K.S., Selkoe, D.J., Christen, Y. (eds) Alzheimer’s Disease: Lessons from Cell Biology. Research and Perspectives in Alzheimer’s Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79423-0_10

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