Tau regulates the localization and function of End binding proteins 1 and 3 (EB1/3) in developing neuronal cells

SAYAS CARMEN L; TORTOSA ELENA; BOLLATI FLAVIA; RAMIREZ-RIOS SACNICTE; ARNAL ISABELLE; AVILA JESUS

JOURNAL OF NEUROCHEMISTRY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2015 vol. 133 p. 653 - 667

0022-3042

The axonal microtubule-associated protein (MAP) tau, is a well-known regulator of microtubule stabilityin neurons. However, the putative interplay between tau and End binding proteins 1 and 3 (EB1/3), thecore microtubule plus-end tracking proteins (+TIPs), has not been elucidated yet. Here, we show that acrosstalk between tau and EB1/3 exists in developing neuronal cells. Tau and EBs partially colocalize atextending neurites of N1E-115 neuroblastoma cells and axons of primary hippocampal neurons, as shownby confocal immunofluorescence analyses. Tau downregulation leads to a reduction of EB1/3 cometlength, as observed in shRNA-stably depleted neuroblastoma cells and TAU-/- neurons. EB1/3 localizationdepends on the expression levels and localization of tau protein. Overexpression of tau at high levelsinduces EBs relocalization to microtubule bundles at extending neurites of N1E-115 cells. Indifferentiating primary neurons, tau is required for the proper accumulation of EBs at stretches ofmicrotubule bundles at the medial and distal regions of the axon. Tau interacts with EB proteins, as shownby immunoprecipitation in different non-neuronal and neuronal cells and in whole brain lysates. Atau/EB1 direct interaction was corroborated by in vitro pull-down assays. FRAP assays performed inneuroblastoma cells confirmed that tau modulates EB3 cellular mobility. In summary, we provideevidence of a new function of tau as a direct regulator of EB proteins in developing neuronal cells. Thiscrosstalk between a classical MAP and a core +TIP may contribute to the fine-tuned regulation of microtubule dynamics and stability during neuronal differentiation.