Premium
Tau regulates the localization and function of End‐binding proteins 1 and 3 in developing neuronal cells
Author(s) -
Sayas Carmen Laura,
Tortosa Elena,
Bollati Flavia,
RamírezRíos Sacnicte,
Arnal Isabelle,
Avila Jesús
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13091
Subject(s) - microtubule , microbiology and biotechnology , neurite , tau protein , immunoprecipitation , colocalization , microtubule associated protein , nocodazole , biology , fluorescence recovery after photobleaching , small hairpin rna , axon , axoplasmic transport , neuroblastoma , chemistry , cell culture , gene knockdown , in vitro , cytoskeleton , cell , biochemistry , genetics , disease , pathology , membrane , alzheimer's disease , medicine
The axonal microtubule‐associated protein tau is a well‐known regulator of microtubule stability in neurons. However, the putative interplay between tau and End‐binding proteins 1 and 3 ( EB 1/3), the core microtubule plus‐end tracking proteins, has not been elucidated yet. Here, we show that a cross‐talk between tau and EB 1/3 exists in developing neuronal cells. Tau and EB s partially colocalize at extending neurites of N1E‐115 neuroblastoma cells and axons of primary hippocampal neurons, as shown by confocal immunofluorescence analyses. Tau down‐regulation leads to a reduction of EB 1/3 comet length, as observed in sh RNA ‐stably depleted neuroblastoma cells and TAU −/− neurons. EB 1/3 localization depends on the expression levels and localization of tau protein. Over‐expression of tau at high levels induces EB s relocalization to microtubule bundles at extending neurites of N1E‐115 cells. In differentiating primary neurons, tau is required for the proper accumulation of EB s at stretches of microtubule bundles at the medial and distal regions of the axon. Tau interacts with EB proteins, as shown by immunoprecipitation in different non‐neuronal and neuronal cells and in whole brain lysates. A tau/ EB 1 direct interaction was corroborated by in vitro pull‐down assays. Fluorescence recovery after photobleaching assays performed in neuroblastoma cells confirmed that tau modulates EB 3 cellular mobility. In summary, we provide evidence of a new function of tau as a direct regulator of EB proteins in developing neuronal cells. This cross‐talk between a classical microtubule‐associated protein and a core microtubule plus‐end tracking protein may contribute to the fine‐tuned regulation of microtubule dynamics and stability during neuronal differentiation.We describe here a novel function for tau as a direct regulator of End binding (EB) proteins in differentiating neuronal cells. EB1/3 cellular mobility and localization in extending neurites and axons is modulated by tau levels and localization. We provide new evidence of the interplay between classical microtubule‐associated proteins (MAPs) and “core” microtubule plus‐end tracking proteins (+TIPs) during neuronal development.