Role of tau in the spatial organization of axonal microtubules: keeping parallel microtubules evenly distributed despite macromolecular crowding.
Fiche publication
Date publication
octobre 2016
Journal
Cellular and molecular life sciences : CMLS
Auteurs
Membres identifiés du Cancéropôle Est :
Dr PIETREMENT Olivier
Tous les auteurs :
Méphon-Gaspard A, Boca M, Pioche-Durieu C, Desforges B, Burgo A, Hamon L, Piétrement O, Pastré D
Lien Pubmed
Résumé
Opposing views have been proposed regarding the role of tau, the principal microtubule-associated protein in axons. On the one hand, tau forms cross-bridges at the interface between microtubules and induces microtubule bundling in neurons. On the other hand, tau is also considered a polymer brush which efficiently separates microtubules. In mature axons, microtubules are indeed arranged in parallel arrays and are well separated from each other. To reconcile these views, we developed a mechanistic model based on in vitro and cellular approaches combined to analytical and numerical analyses. The results indicate that tau forms long-range cross-bridges between microtubules under macromolecular crowding conditions. Tau cross-bridges prevent the redistribution of tau away from the interface between microtubules, which would have occurred in the polymer brush model. Consequently, the short-range attractive force between microtubules induced by macromolecular crowding is avoided and thus microtubules remain well separated from each other. Interestingly, in this unified model, tau diffusion on microtubules enables to keep microtubules evenly distributed in axonal sections at low tau levels.
Mots clés
Alzheimer, Cytoskeleton, Neuron, Tauopathy
Référence
Cell. Mol. Life Sci.. 2016 10;73(19):3745-60