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Oncotarget. 2015 Dec 22;6(41):43557-70. doi: 10.18632/oncotarget.6196.

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

Author information

Inserm U981, Institut Gustave Roussy Department of Molecular Medicine, Villejuif, France.
Université Paris-Saclay, Villejuif, France.
CNRS UMR8104, Institut Cochin, Paris, France.
Cell Biology, Faculty of Science, Utrecht University, Padualaan, CH Utrecht, The Netherlands.
Cell and Tissue Imaging Core Facilty, PICT-IBiSA, CNRS UMR144 Institut Curie, Centre de Recherche, Paris, France.
Inserm U836, Grenoble Institut des Neurosciences, Grenoble, France.
Aix Marseille Université, Inserm, CRO2 UMR_S 911, Marseille, France.
APHM, Hôpital Timone, Marseille, France.
Scientific Partnerships Roche SAS, Boulogne Billancourt, France.


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.


+TIP; EB1; MTUS1; microtubule dynamics; protein interaction

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