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

Sacnicte Ramirez-Rios; Eric Denarier; Elea Prezel; Angélique Vinit; Virginie Stoppin-Mellet; François Devred; Pascale Barbier; Vincent Peyrot; Carmen Laura Sayas; Jesús 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

Sacnicte Ramirez-Rios ¹ Eric Denarier ² Elea Prezel ¹ Angélique Vinit ¹ Virginie Stoppin-Mellet ^{3, 4} François Devred ⁵ Pascale Barbier ⁵ Vincent Peyrot ⁵ Carmen Laura Sayas ⁶ Jesús Avila ⁷ Leticia Peris ^{8, 1} Annie Andrieux ^{3, 4} Laurence Serre ⁹ Anne Fourest-Lieuvin ^{1, 8} Isabelle Arnal ¹

1 GIN - Grenoble Institut des Neurosciences

2 Laboratory of Developmental Biology

3 INSERM U836, équipe 1, Physiopathologie du cytosquelette

GPC - Groupe Physiopathologie du Cytosquelette, GIN - Grenoble Institut des Neurosciences

4 LPCV - Laboratoire de physiologie cellulaire végétale

5 CRO2 - Centre de Recherches en Oncologie biologique et Oncopharmacologie

6 ULL - Universidad de La Laguna [Tenerife - SP]

7 CBM Severo Ochoa

8 GPC - Groupe Physiopathologie du Cytosquelette

9 LPM - Laboratoire des Protéines Membranaires

IBS - UMR 5075 - Institut de biologie structurale

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.

Keywords : phosphorylation EB1 microtubule tau

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Neurons and Cognition [q-bio.NC] / Neurobiology

Life Sciences [q-bio] / Biochemistry, Molecular Biology

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22 Mol. Biol. Cell-2016.pdf

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

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