Negative regulation of EB1 turnover at microtubule plus ends by interaction with microtubule-associated protein ATIP3

Abstract : The regulation of microtubule dynamics is critical to ensure essential cell functions. End binding protein 1 (EB1) is a master regulator of microtubule dynamics that autonomously binds an extended GTP/GDP-Pi structure at growing microtubule ends and recruits regulatory proteins at this location. However, negative regulation of EB1 association with growing microtubule ends remains poorly understood. We show here that microtubule-associated tumor suppressor ATIP3 interacts with EB1 through direct binding of a non-canonical proline-rich motif. Results indicate that ATIP3 does not localize at growing microtubule ends and that in situ ATIP3-EB1 molecular complexes are mostly detected in the cytosol. We present evidence that a minimal EB1-interacting sequence of ATIP3 is both necessary and sufficient to prevent EB1 accumulation at growing microtubule ends in living cells and that EB1-interaction is involved in reducing cell polarity. By fluorescence recovery of EB1-GFP after photobleaching, we show that ATIP3 silencing accelerates EB1 turnover at microtubule ends with no modification of EB1 diffusion in the cytosol. We propose a novel mechanism by which ATIP3-EB1 interaction indirectly reduces the kinetics of EB1 exchange on its recognition site, thereby accounting for negative regulation of microtubule dynamic instability. Our findings provide a unique example of decreased EB1 turnover at growing microtubule ends by cytosolic interaction with a tumor suppressor. INTRODUCTION Microtubules (MTs) are polarized structures that continuously switch between periods of polymerization and depolymerization at their growing (plus) ends. This process, termed MT dynamic instability, allows rapid reorganization of the MT cytoskeleton during essential cell functions such as cell polarity and migration, mitosis
Type de document :
Article dans une revue
Oncotarget, Impact journals, 2015, 6 (41), pp.43557-43570. 〈10.18632/oncotarget.6196〉
Liste complète des métadonnées

Littérature citée [36 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-01223890
Contributeur : Mireille Bos <>
Soumis le : mardi 3 novembre 2015 - 16:04:33
Dernière modification le : vendredi 31 août 2018 - 09:18:24
Document(s) archivé(s) le : jeudi 4 février 2016 - 11:17:15

Fichier

6196-87766-3-PB.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Citation

Lauriane Velot, Angie Molina, Sylvie Rodrigues-Ferreira, Anne Nehlig, Benjamin Pierre Bouchet, et al.. Negative regulation of EB1 turnover at microtubule plus ends by interaction with microtubule-associated protein ATIP3. Oncotarget, Impact journals, 2015, 6 (41), pp.43557-43570. 〈10.18632/oncotarget.6196〉. 〈inserm-01223890〉

Partager

Métriques

Consultations de la notice

645

Téléchargements de fichiers

172