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Mol Biol Cell. 2018 Jan 15;29(2):154-165. doi: 10.1091/mbc.E17-06-0429. Epub 2017 Nov 22.

Tau can switch microtubule network organizations: from random networks to dynamic and stable bundles.

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Inserm, U1216, Université Grenoble Alpes.
Grenoble Institut des Neurosciences, Université Grenoble Alpes.
Centre National de la Recherche Scientifique, Grenoble Institut des Neurosci ences, Institut de Biosciences et Biotechnologies de Grenoble, F-38000 Grenoble, France.
Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut de Biosciences et Biotechnologies de Grenoble, F-38000 Grenoble, France.
Inserm, U1216, Université Grenoble Alpes


In neurons, microtubule networks alternate between single filaments and bundled arrays under the influence of effectors controlling their dynamics and organization. Tau is a microtubule bundler that stabilizes microtubules by stimulating growth and inhibiting shrinkage. The mechanisms by which tau organizes microtubule networks remain poorly understood. Here, we studied the self-organization of microtubules growing in the presence of tau isoforms and mutants. The results show that tau's ability to induce stable microtubule bundles requires two hexapeptides located in its microtubule-binding domain and is modulated by its projection domain. Site-specific pseudophosphorylation of tau promotes distinct microtubule organizations: stable single microtubules, stable bundles, or dynamic bundles. Disease-related tau mutations increase the formation of highly dynamic bundles. Finally, cryo-electron microscopy experiments indicate that tau and its variants similarly change the microtubule lattice structure by increasing both the protofilament number and lattice defects. Overall, our results uncover novel phosphodependent mechanisms governing tau's ability to trigger microtubule organization and reveal that disease-related modifications of tau promote specific microtubule organizations that may have a deleterious impact during neurodegeneration.

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