Tau antagonizes end-binding protein tracking at microtubule ends through a phosphorylation-dependent mechanism.
Sacnicte Ramirez-Rios, Eric Denarier, Eléa Prezel, Angélique Vinit, Virginie Stoppin-Mellet, François Devred, Pascale Barbier, Vincent Peyrot, Carmen Laura Sayas, Jesus Avila, Leticia Peris, Annie Andrieux, Laurence Serre, Anne Fourest-Lieuvin, Isabelle Arnal
Molecular biology of the cell 2016 Oct 1Proper regulation of microtubule dynamics is essential for cell functions and involves various microtubule-associated proteins (MAPs). Among them, end-binding proteins (EBs) accumulate at microtubule plus ends, whereas structural MAPs bind along the microtubule lattice. Recent data indicate that the structural MAP tau modulates EB subcellular localization in neurons. However, the molecular determinants of EB/tau interaction remain unknown, as is the effect of this interplay on microtubule dynamics. Here we investigate the mechanisms governing EB/tau interaction in cell-free systems and cellular models. We find that tau inhibits EB tracking at microtubule ends. Tau and EBs form a complex via the C-terminal region of EBs and the microtubule-binding sites of tau. These two domains are required for the inhibitory activity of tau on EB localization to microtubule ends. Moreover, the phosphomimetic mutation S262E within tau microtubule-binding sites impairs EB/tau interaction and prevents the inhibitory effect of tau on EB comets. We further show that microtubule dynamic parameters vary, depending on the combined activities of EBs and tau proteins. Overall our results demonstrate that tau directly antagonizes EB function through a phosphorylation-dependent mechanism. This study highlights a novel role for tau in EB regulation, which might be impaired in neurodegenerative disorders. © 2016 Ramirez-Rios et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
Citation
Sacnicte Ramirez-Rios, Eric Denarier, Eléa Prezel, Angélique Vinit, Virginie Stoppin-Mellet, François Devred, Pascale Barbier, Vincent Peyrot, Carmen Laura Sayas, Jesus Avila, Leticia Peris, Annie Andrieux, Laurence Serre, Anne Fourest-Lieuvin, Isabelle Arnal. Tau antagonizes end-binding protein tracking at microtubule ends through a phosphorylation-dependent mechanism. Molecular biology of the cell. 2016 Oct 1;27(19):2924-34
PMID: 27466319
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