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Nat Cell Biol. 2019 Sep;21(9):1086-1092. doi: 10.1038/s41556-019-0374-6. Epub 2019 Sep 2.

Kinetically distinct phases of tau on microtubules regulate kinesin motors and severing enzymes.

Author information

1
Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Prague West, Czech Republic.
2
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
3
Cluster of Excellence Physics of Life, Technische Universität Dresden, Dresden, Germany.
4
B CUBE-Center for Molecular Bioengineering, Technische Universität Dresden, Dresden, Germany.
5
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany. hernande@mpicbg.de.
6
Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Prague West, Czech Republic. zdenek.lansky@ibt.cas.cz.
7
Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Prague West, Czech Republic. marcus.braun@ibt.cas.cz.
8
B CUBE-Center for Molecular Bioengineering, Technische Universität Dresden, Dresden, Germany. marcus.braun@ibt.cas.cz.

Abstract

Tau is an intrinsically disordered protein, which diffuses on microtubules1. In neurodegenerative diseases, collectively termed tauopathies, malfunction of tau and its detachment from axonal microtubules are correlated with axonal degeneration2. Tau can protect microtubules from microtubule-degrading enzymes such as katanin3. However, how tau carries out this regulatory function is still unclear. Here, using in vitro reconstitution, we show that tau molecules on microtubules cooperatively form cohesive islands that are kinetically distinct from tau molecules that individually diffuse on microtubules. Dependent on the tau concentration in solution, the islands reversibly grow or shrink by addition or release of tau molecules at their boundaries. Shielding microtubules from kinesin-1 motors and katanin, the islands exhibit regulatory qualities distinct from a comparably dense layer of diffusible tau. Superprocessive kinesin-8 motors penetrate the islands and cause their disassembly. Our results reveal a microtubule-dependent phase of tau that constitutes an adaptable protective layer on the microtubule surface. We anticipate that other intrinsically disordered axonal proteins display a similar cooperative behaviour and potentially compete with tau in regulating access to the microtubule surface.

PMID:
31481789
DOI:
10.1038/s41556-019-0374-6

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