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Transport and diffusion of Tau protein in neurons

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Abstract

In highly polarized and elongated cells such as neurons, Tau protein must enter and move down the axon to fulfill its biological task of stabilizing axonal microtubules. Therefore, cellular systems for distributing Tau molecules are needed. This review discusses different mechanisms that have been proposed to contribute to the dispersion of Tau molecules in neurons. They include (1) directed transport along microtubules as cargo of tubulin complexes and/or motor proteins, (2) diffusion, either through the cytosolic space or along microtubules, and (3) mRNA-based mechanisms such as transport of Tau mRNA into axons and local translation. Diffusion along the microtubule lattice or through the cytosol appear to be the major mechanisms for axonal distribution of Tau protein in the short-to-intermediate range over distances of up to a millimetre. The high diffusion coefficients ensure that Tau can distribute evenly throughout the axonal volume as well as along microtubules. Motor protein-dependent transport of Tau dominates over longer distances and time scales. At low near-physiological levels, Tau is co-transported along with short microtubules from cell bodies into axons by cytoplasmic dynein and kinesin family members at rates of slow axonal transport.

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Abbreviations

3′UTR:

3′ Untranslated region

aa:

Amino acids

CNS:

Central nervous system

FRAP:

Fluorescence recovery after photobleaching

FTDP17:

Fronto-temporal dementia and Parkinsonism linked to chromosome 17

JIP1:

c-Jun N-terminal kinase-interacting protein 1

MAP:

Microtubule-associated protein

PARPs:

Periaxoplasmic ribosomal plaques

PHF:

Paired helical filaments

PP1:

Protein phosphatase 1

RNP:

Ribonucleoprotein

TIRF:

Total internal reflection fluorescence

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Acknowledgments

Work performed in the Scholz or Mandelkow groups was partially supported by Deutsche Forschungsgemeinschaft (DFG) Research Unit FOR629 grants to T.S and E.M. We thank Dietmar J. Manstein for organizing Research Unit FOR629 as well as Walter Steffen and Bernhard Brenner for helpful discussions.

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Authors and Affiliations

  1. Institute for Molecular and Cell Physiology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany

    Tim Scholz

  2. DZNE, German Center for Neurodegenerative Diseases, 53175, Bonn, Germany

    Eckhard Mandelkow

  3. CAESAR Research Center, Ludwig-Erhard-Allee 2, 53175, Bonn, Germany

    Eckhard Mandelkow

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  1. Tim Scholz
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  2. Eckhard Mandelkow
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Correspondence to Tim Scholz.

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Scholz, T., Mandelkow, E. Transport and diffusion of Tau protein in neurons. Cell. Mol. Life Sci. 71, 3139–3150 (2014). https://doi.org/10.1007/s00018-014-1610-7

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  • DOI: https://doi.org/10.1007/s00018-014-1610-7

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