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.
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Abbreviations
- APC:
-
Adenomatous polyposis coli
- ATIP:
-
AT2 receptor-interacting protein
- CAP-Gly:
-
Cytoskeletal-associated protein glycine-rich
- Cdk:
-
Cyclin-dependent kinase
- CH:
-
Calponin homology
- CLIP:
-
Cytoplasmic linker protein
- DDA3:
-
Differential display activated by p53
- EB:
-
End-binding protein
- EBH:
-
End-binding homology
- GDP:
-
Guanosine diphosphate
- GSK3β:
-
Glycogen synthase kinase 3 beta
- GTP:
-
Guanosine triphosphate
- KIF2A:
-
Kinesin heavy chain member 2A
- MAP:
-
Microtubule-associated protein
- MAPRE:
-
Microtubule-associated protein RP/EB
- MCAK:
-
Mitotic centromere-associated kinesin
- MT:
-
Microtubule
- MTA:
-
Microtubule-targeting agent
- NMDA:
-
N-Methyl-d-aspartate
- PCAF:
-
P300/CBP-associated factor
- Pi:
-
Inorganic phosphate
- PI3K:
-
Phosphoinositide 3-kinase
- PP2A:
-
Protein phosphatase 2
- ROS:
-
Reactive oxygen species
- SxIP:
-
Serine-any amino acid–isoleucine–proline
- +TIP:
-
Microtubule plus end-tracking protein
- TTBK:
-
Tau-tubulin kinase
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Acknowledgements
Authors are supported by grants from the Institut Gustave Roussy, the Inserm, the CNRS, the Ligue contre le Cancer Comité Ile-de-France, the Association pour la Recherche contre le Cancer (Fondation ARC), the A*MIDEX project (n°ANR-11-IDEX-0001-02) funded by the “Investissements d’Avenir” French Government program, managed by the ANR and ITMO Cancer AVIESAN as part of the Cancer Plan No. PC201419, and the associations Odyssea and Prolific.
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Nehlig, A., Molina, A., Rodrigues-Ferreira, S. et al. Regulation of end-binding protein EB1 in the control of microtubule dynamics. Cell. Mol. Life Sci. 74, 2381–2393 (2017). https://doi.org/10.1007/s00018-017-2476-2
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DOI: https://doi.org/10.1007/s00018-017-2476-2