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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.

SUBMITTER: Velot L 

PROVIDER: S-EPMC4791250 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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

Velot Lauriane L   Molina Angie A   Rodrigues-Ferreira Sylvie S   Nehlig Anne A   Bouchet Benjamin Pierre BP   Morel Marina M   Leconte Ludovic L   Serre Laurence L   Arnal Isabelle I   Braguer Diane D   Savina Ariel A   Honore Stéphane S   Nahmias Clara C  

Oncotarget 20151201 41


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  ...[more]

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