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Cell Mol Life Sci. 2017 Jul;74(13):2381-2393. doi: 10.1007/s00018-017-2476-2. Epub 2017 Feb 15.

Regulation of end-binding protein EB1 in the control of microtubule dynamics.

Author information

1
Inserm U981, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94800, Villejuif, France.
2
University Paris Saclay, 94800, Villejuif, France.
3
CBD, University of Toulouse-3, Toulouse, France.
4
Aix Marseille University, Inserm U-911, CRO2, Marseille, France.
5
Service Pharmacie, CHU Hôpital de La Timone, APHM, Marseille, France.
6
Inserm U981, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94800, Villejuif, France. clara.nahmias@inserm.fr.
7
University Paris Saclay, 94800, Villejuif, France. clara.nahmias@inserm.fr.

Abstract

The regulation of microtubule dynamics is critical to ensure essential cell functions, such as proper segregation of chromosomes during mitosis or cell polarity and migration. End-binding protein 1 (EB1) is a plus-end-tracking protein (+TIP) that accumulates at growing microtubule ends and plays a pivotal role in the regulation of microtubule dynamics. EB1 autonomously binds an extended tubulin-GTP/GDP-Pi structure at growing microtubule ends and acts as a molecular scaffold that recruits a large number of regulatory +TIPs through interaction with CAP-Gly or SxIP motifs. While extensive studies have focused on the structure of EB1-interacting site at microtubule ends and its role as a molecular platform, the mechanisms involved in the negative regulation of EB1 have only started to emerge and remain poorly understood. In this review, we summarize recent studies showing that EB1 association with MT ends is regulated by post-translational modifications and affected by microtubule-targeting agents. We also present recent findings that structural MAPs, that have no tip-tracking activity, physically interact with EB1 to prevent its accumulation at microtubule plus ends. These observations point out a novel concept of "endogenous EB1 antagonists" and emphasize the importance of finely regulating EB1 function at growing microtubule ends.

KEYWORDS:

+TIP; EB1; EB3; MAPs; Microtubule-targeting agents; Phosphorylation

PMID:
28204846
DOI:
10.1007/s00018-017-2476-2
[Indexed for MEDLINE]

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