title: Role of tau in the spatial organization of axonal microtubules: keeping parallel microtubules evenly distributed despite macromolecular crowding.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR1204, Université Evry-Val d'Essonne, Evry, 91025, France.
authors.forename: Alix
authors.initials: A
authors.lastname: Méphon-Gaspard
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR1204, Université Evry-Val d'Essonne, Evry, 91025, France.
authors.forename: Mirela
authors.initials: M
authors.lastname: Boca
authors.affiliation: UMR 8126, CNRS, Gustave Roussy Université Paris Sud, Université Paris-Saclay, Villejuif, 94805, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Pioche-Durieu
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR1204, Université Evry-Val d'Essonne, Evry, 91025, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Desforges
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR1204, Université Evry-Val d'Essonne, Evry, 91025, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Burgo
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR1204, Université Evry-Val d'Essonne, Evry, 91025, France.
authors.forename: Loic
authors.initials: L
authors.lastname: Hamon
authors.affiliation: UMR 8126, CNRS, Gustave Roussy Université Paris Sud, Université Paris-Saclay, Villejuif, 94805, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Piétrement
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR1204, Université Evry-Val d'Essonne, Evry, 91025, France. david.pastre@univ-evry.fr.
authors.forename: David
authors.initials: D
authors.lastname: Pastré
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003198:Computer Simulation; D004058:Diffusion; D005453:Fluorescence; D046911:Macromolecular Substances; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D000072417:Protein Domains; D014404:Tubulin / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D046911:Macromolecular Substances; D014404:Tubulin; D016875:tau Proteins
keywords: Alzheimer; Cytoskeleton; Neuron; Tauopathy