Oncotarget

Research Papers:

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

Lauriane Velot, Angie Molina, Sylvie Rodrigues-Ferreira, Anne Nehlig, Benjamin Pierre Bouchet, Marina Morel, Ludovic Leconte, Laurence Serre, Isabelle Arnal, Diane Braguer, Ariel Savina, Stéphane Honore and Clara Nahmias _

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Oncotarget. 2015; 6:43557-43570. https://doi.org/10.18632/oncotarget.6196

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Abstract

Lauriane Velot1,2,3,*, Angie Molina1,2,3,*, Sylvie Rodrigues-Ferreira1,2,3, Anne Nehlig1,2, Benjamin Pierre Bouchet4, Marina Morel3, Ludovic Leconte5, Laurence Serre6, Isabelle Arnal6, Diane Braguer7,8, Ariel Savina9, Stéphane Honore7,8 and Clara Nahmias1,2,3

1 Inserm U981, Institut Gustave Roussy Department of Molecular Medicine, Villejuif, France

2 Université Paris-Saclay, Villejuif, France

3 CNRS UMR8104, Institut Cochin, Paris, France

4 Cell Biology, Faculty of Science, Utrecht University, Padualaan, CH Utrecht, The Netherlands

5 Cell and Tissue Imaging Core Facilty, PICT-IBiSA, CNRS UMR144 Institut Curie, Centre de Recherche, Paris, France

6 Inserm U836, Grenoble Institut des Neurosciences, Grenoble, France

7 Aix Marseille Université, Inserm, CRO2 UMR_S 911, Marseille, France

8 APHM, Hôpital Timone, Marseille, France

9 Scientific Partnerships Roche SAS, Boulogne Billancourt, France

* These authors have contributed equally to this work

Correspondence to:

Clara Nahmias, email:

Keywords: EB1, MTUS1, protein interaction, +TIP, microtubule dynamics

Received: May 07, 2015 Accepted: October 14, 2015 Published: October 20, 2015

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.


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