Tau antagonizes end-binding protein tracking at microtubule ends through a phosphorylation- dependent mechanism

Abstract : Proper 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 microtu-bule lattice. Recent data indicate that the structural MAP tau modulates EB subcellular local-ization 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 phos-phomimetic 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 phos-phorylation-dependent mechanism. This study highlights a novel role for tau in EB regulation, which might be impaired in neurodegenerative disorders.
Complete list of metadatas

Cited literature [42 references]  Display  Hide  Download

https://hal-amu.archives-ouvertes.fr/hal-01478521
Contributor : François Devred <>
Submitted on : Tuesday, February 28, 2017 - 11:00:00 AM
Last modification on : Thursday, April 4, 2019 - 1:08:03 PM
Long-term archiving on : Monday, May 29, 2017 - 1:10:18 PM

File

22 Mol. Biol. Cell-2016.pdf
Explicit agreement for this submission

Identifiers

Collections

Citation

Sacnicte Ramirez-Rios, Eric Denarier, Elea Prezel, Angélique Vinit, Virginie Stoppin-Mellet, et al.. Tau antagonizes end-binding protein tracking at microtubule ends through a phosphorylation- dependent mechanism. Molecular Biology of the Cell, American Society for Cell Biology, 2016, 27 (19), pp.2924-2934. ⟨10.1091/mbc.E16-01-0029)⟩. ⟨hal-01478521⟩

Share

Metrics

Record views

666

Files downloads

132