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Mechanisms of Axonal Sorting of Tau and Influence of the Axon Initial Segment on Tau Cell Polarity

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Tau Biology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1184))

Abstract

Tau is a microtubule-associated protein (MAP) that is mainly sorted into the axons in physiological conditions, but missorted in Alzheimer Disease and related tauopathies. The mechanism(s) of axonal targeting of Tau protein are still a matter of debate. Several possibilities for the axonal localization of Tau protein have been proposed: (1) Targeting of Tau mRNA into axons which is then translated locally. (2) Preferred axonal translation of Tau mRNA. (3) Specific dendritic degradation of Tau protein. (4) Active axonal sorting of somatically translated Tau protein. (5) Axonal retention of Tau protein by specific association of Tau protein with axonal structures, namely particularly modified microtubules. (6) Restriction of Tau diffusion by a selective filter function of the Axon Initial Segment (AIS). In our research we focused on the Tau Diffusion Barrier (TDB), located within the AIS, which controls anterograde and retrograde propagation of Tau. It shows both sensitivity to size of the Tau protein isoforms, and to disruption of the molecular structure of the AIS. Here, we review proposed mechanisms of axonal targeting of Tau and potential influences of the TDB/AIS on the subcellular distribution of Tau.

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Acknowledgments

This work was supported by the Cologne Fortune Program/Faculty of Medicine, University of Cologne (HZ) and the German Center for Neurodegenerative Diseases (DZNE) and CAESAR/Max-Planck-Society (MPG) (EM). We are grateful to Julia Lüdtke for excellent technical assistance and Dr. Eva-Maria Mandelkow for stimulating discussions throughout this project.

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Authors and Affiliations

  1. Institute of Human Genetics, University of Cologne, Cologne, Germany

    Hans Zempel

  2. Faculty of Medicine, University Hospital Cologne, Cologne, Germany

    Hans Zempel

  3. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany

    Hans Zempel

  4. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

    Eckhard Mandelkow

  5. CAESAR Research Center, Max-Planck-Society, Bonn, Germany

    Eckhard Mandelkow

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  1. Hans Zempel
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  2. Eckhard Mandelkow
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Correspondence to Hans Zempel or Eckhard Mandelkow .

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Editors and Affiliations

  1. Department of Life Sciences, Gakushuin University, Tokyo, Japan

    Akihiko Takashima

  2. Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA

    Benjamin Wolozin

  3. University of Lille, INSERM, CHU-Lille, Alzheimer & Tauopathies, LabEx DISTALZ, Lille, France

    Luc Buee

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Zempel, H., Mandelkow, E. (2019). Mechanisms of Axonal Sorting of Tau and Influence of the Axon Initial Segment on Tau Cell Polarity. In: Takashima, A., Wolozin, B., Buee, L. (eds) Tau Biology. Advances in Experimental Medicine and Biology, vol 1184. Springer, Singapore. https://doi.org/10.1007/978-981-32-9358-8_6

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