Skip to main content

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

Cellular and Molecular Life Sciences volume 74, pages 2381–2393 (2017)Cite this article

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.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

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

References

  1. Hyman AA, Salser S, Drechsel DN et al (1992) Role of GTP hydrolysis in microtubule dynamics: information from a slowly hydrolyzable analogue, GMPCPP. Mol Biol Cell 3:1155–1167

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Akhmanova A, Steinmetz MO (2015) Control of microtubule organization and dynamics: two ends in the limelight. Nat Rev Mol Cell Biol 16:711–726. doi:10.1038/nrm4084

    CAS  Article  PubMed  Google Scholar 

  3. Mitchison T, Kirschner M (1984) Dynamic instability of microtubule growth. Nature 312:237–242. doi:10.1038/312237a0

    CAS  Article  PubMed  Google Scholar 

  4. Desai A, Mitchison TJ (1997) Microtubule polymerization dynamics. Annu Rev Cell Dev Biol 13:83–117. doi:10.1146/annurev.cellbio.13.1.83

    CAS  Article  PubMed  Google Scholar 

  5. Howard J, Hyman AA (2003) Dynamics and mechanics of the microtubule plus end. Nature 422:753–758. doi:10.1038/nature01600

    CAS  Article  PubMed  Google Scholar 

  6. Akhmanova A, Steinmetz MO (2008) Tracking the ends: a dynamic protein network controls the fate of microtubule tips. Nat Rev Mol Cell Biol 9:309–322. doi:10.1038/nrm2369

    CAS  Article  PubMed  Google Scholar 

  7. Seetapun D, Castle BT, McIntyre AJ et al (2012) Estimating the microtubule GTP cap size in vivo. Curr Biol 22:1681–1687. doi:10.1016/j.cub.2012.06.068

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Bowne-Anderson H, Hibbel A, Howard J (2015) Regulation of microtubule growth and catastrophe: unifying theory and experiment. Trends Cell Biol 25:769–779. doi:10.1016/j.tcb.2015.08.009

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. Piedra F-A, Kim T, Garza ES et al (2016) GDP to GTP exchange on the microtubule end can contribute to the frequency of catastrophe. Mol Biol Cell 27:3515–3525. doi:10.1091/mbc.E16-03-0199

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. Duellberg C, Cade NI, Holmes D, Surrey T (2016) The size of the EB cap determines instantaneous microtubule stability. eLife 5:e13470. doi:10.7554/eLife.13470

    Article  PubMed  PubMed Central  Google Scholar 

  11. Su LK, Burrell M, Hill DE et al (1995) APC binds to the novel protein EB1. Cancer Res 55:2972–2977

    CAS  PubMed  Google Scholar 

  12. Su L-K, Qi Y (2001) Characterization of human MAPRE genes and their proteins. Genomics 71:142–149. doi:10.1006/geno.2000.6428

    CAS  Article  PubMed  Google Scholar 

  13. Nakagawa H, Koyama K, Murata Y et al (2000) EB3, a novel member of the EB1 family preferentially expressed in the central nervous system, binds to a CNS-specific APC homologue. Oncogene 19:210–216. doi:10.1038/sj.onc.1203308

    CAS  Article  PubMed  Google Scholar 

  14. Komarova Y, De Groot CO, Grigoriev I et al (2009) Mammalian end binding proteins control persistent microtubule growth. J Cell Biol 184:691–706. doi:10.1083/jcb.200807179

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. De Groot CO, Jelesarov I, Damberger FF et al (2010) Molecular insights into Mammalian end-binding protein heterodimerization. J Biol Chem 285:5802–5814. doi:10.1074/jbc.M109.068130

    Article  PubMed  Google Scholar 

  16. Sen I, Veprintsev D, Akhmanova A, Steinmetz MO (2013) End binding proteins are obligatory dimers. PloS One 8:e74448. doi:10.1371/journal.pone.0074448

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. Jiang K, Toedt G, Montenegro Gouveia S et al (2012) A proteome-wide screen for Mammalian SxIP Motif-containing microtubule plus-end tracking proteins. Curr Biol 22:1800–1807. doi:10.1016/j.cub.2012.07.047

    CAS  Article  PubMed  Google Scholar 

  18. Piehl M (2003) Organization and dynamics of growing microtubule plus ends during early mitosis. Mol Biol Cell 14:916–925. doi:10.1091/mbc.E02-09-0607

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Stepanova T, Slemmer J, Hoogenraad CC et al (2003) Visualization of microtubule growth in cultured neurons via the use of EB3-GFP (end-binding protein 3-green fluorescent protein). J Neurosci Off J Soc Neurosci 23:2655–2664

    CAS  Google Scholar 

  20. Salaycik KJ (2005) Quantification of microtubule nucleation, growth and dynamics in wound-edge cells. J Cell Sci 118:4113–4122. doi:10.1242/jcs.02531

    CAS  Article  PubMed  Google Scholar 

  21. Bieling P, Laan L, Schek H et al (2007) Reconstitution of a microtubule plus-end tracking system in vitro. Nature 450:1100–1105. doi:10.1038/nature06386

    CAS  Article  PubMed  Google Scholar 

  22. Dixit R, Barnett B, Lazarus JE, et al (2009) Microtubule plus-end tracking by CLIP-170 requires EB1. Proc Natl Acad Sci 106:492–497. doi:10.1073/pnas.0807614106

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Maurer SP, Bieling P, Cope J et al (2011) GTP S microtubules mimic the growing microtubule end structure recognized by end-binding proteins (EBs). Proc Natl Acad Sci 108:3988–3993. doi:10.1073/pnas.1014758108

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Dragestein KA, van Cappellen WA, van Haren J et al (2008) Dynamic behavior of GFP–CLIP-170 reveals fast protein turnover on microtubule plus ends. J Cell Biol 180:729–737. doi:10.1083/jcb.200707203

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. Zanic M, Stear JH, Hyman AA, Howard J (2009) EB1 recognizes the nucleotide state of tubulin in the microtubule lattice. PLoS One 4:e7585. doi:10.1371/journal.pone.0007585

    Article  PubMed  PubMed Central  Google Scholar 

  26. Maurer SP, Fourniol FJ, Bohner G et al (2012) EBs recognize a nucleotide-dependent structural cap at growing microtubule ends. Cell 149:371–382. doi:10.1016/j.cell.2012.02.049

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. Zhang R, Alushin GM, Brown A, Nogales E (2015) Mechanistic origin of microtubule dynamic instability and its modulation by EB proteins. Cell 162:849–859. doi:10.1016/j.cell.2015.07.012

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. Guesdon A, Bazile F, Buey RM et al (2016) EB1 interacts with outwardly curved and straight regions of the microtubule lattice. Nat Cell Biol 18:1102–1108. doi:10.1038/ncb3412

    CAS  Article  PubMed  Google Scholar 

  29. Maurer SP, Cade NI, Bohner G et al (2014) EB1 accelerates two conformational transitions important for microtubule maturation and dynamics. Curr Biol 24:372–384. doi:10.1016/j.cub.2013.12.042

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. Vitre B, Coquelle FM, Heichette C et al (2008) EB1 regulates microtubule dynamics and tubulin sheet closure in vitro. Nat Cell Biol 10:415–421. doi:10.1038/ncb1703

    CAS  Article  PubMed  Google Scholar 

  31. Zanic M, Widlund PO, Hyman AA, Howard J (2013) Synergy between XMAP215 and EB1 increases microtubule growth rates to physiological levels. Nat Cell Biol 15:688–693. doi:10.1038/ncb2744

    CAS  Article  PubMed  Google Scholar 

  32. Mohan R, Katrukha EA, Doodhi H et al (2013) End-binding proteins sensitize microtubules to the action of microtubule-targeting agents. Proc Natl Acad Sci 110:8900–8905. doi:10.1073/pnas.1300395110

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. Galjart N (2010) Plus-end-tracking proteins and their interactions at microtubule ends. Curr Biol 20:R528–R537. doi:10.1016/j.cub.2010.05.022

    CAS  Article  PubMed  Google Scholar 

  34. Akhmanova A, Steinmetz MO (2010) Microtubule +TIPs at a glance. J Cell Sci 123:3415–3419. doi:10.1242/jcs.062414

    CAS  Article  PubMed  Google Scholar 

  35. Kumar P, Wittmann T (2012) +TIPs: SxIPping along microtubule ends. Trends Cell Biol 22:418–428. doi:10.1016/j.tcb.2012.05.005

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. Honnappa S, Gouveia SM, Weisbrich A et al (2009) An EB1-binding motif acts as a microtubule tip localization signal. Cell 138:366–376. doi:10.1016/j.cell.2009.04.065

    CAS  Article  PubMed  Google Scholar 

  37. Buey RM, Sen I, Kortt O et al (2012) Sequence determinants of a microtubule tip localization signal (MtLS). J Biol Chem 287:28227–28242. doi:10.1074/jbc.M112.373928

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  38. Tamura N, Simon JE, Nayak A et al (2015) A proteomic study of mitotic phase-specific interactors of EB1 reveals a role for SXIP-mediated protein interactions in anaphase onset. Biol Open 4:155–169. doi:10.1242/bio.201410413

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. Schwanhäusser B, Busse D, Li N et al (2011) Global quantification of mammalian gene expression control. Nature 473:337–342. doi:10.1038/nature10098

    Article  PubMed  Google Scholar 

  40. Nagaraj N, Wisniewski JR, Geiger T et al (2014) Deep proteome and transcriptome mapping of a human cancer cell line. Mol Syst Biol 7:548–548. doi:10.1038/msb.2011.81

    Article  Google Scholar 

  41. Beck M, Schmidt A, Malmstroem J et al (2014) The quantitative proteome of a human cell line. Mol Syst Biol 7:549–549. doi:10.1038/msb.2011.82

    Article  Google Scholar 

  42. Jiang K, Akhmanova A (2011) Microtubule tip-interacting proteins: a view from both ends. Curr Opin Cell Biol 23:94–101. doi:10.1016/j.ceb.2010.08.008

    CAS  Article  PubMed  Google Scholar 

  43. Jiang K, Wang J, Liu J et al (2009) TIP150 interacts with and targets MCAK at the microtubule plus ends. EMBO Rep 10:857–865. doi:10.1038/embor.2009.94

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. van der Vaart B, Manatschal C, Grigoriev I et al (2011) SLAIN2 links microtubule plus end–tracking proteins and controls microtubule growth in interphase. J Cell Biol 193:1083–1099. doi:10.1083/jcb.201012179

    Article  PubMed  PubMed Central  Google Scholar 

  45. Duellberg C, Trokter M, Jha R et al (2014) Reconstitution of a hierarchical +TIP interaction network controlling microtubule end tracking of dynein. Nat Cell Biol 16:804–811. doi:10.1038/ncb2999

    CAS  Article  PubMed  Google Scholar 

  46. Zimniak T, Stengl K, Mechtler K, Westermann S (2009) Phosphoregulation of the budding yeast EB1 homologue Bim1p by Aurora/Ipl1p. J Cell Biol 186:379–391. doi:10.1083/jcb.200901036

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  47. Iimori M, Ozaki K, Chikashige Y et al (2012) A mutation of the fission yeast EB1 overcomes negative regulation by phosphorylation and stabilizes microtubules. Exp Cell Res 318:262–275. doi:10.1016/j.yexcr.2011.11.006

    CAS  Article  PubMed  Google Scholar 

  48. Ban R, Matsuzaki H, Akashi T et al (2009) Mitotic regulation of the stability of microtubule plus-end tracking protein EB3 by ubiquitin ligase SIAH-1 and aurora mitotic kinases. J Biol Chem 284:28367–28381. doi:10.1074/jbc.M109.000273

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  49. Ferreira JG, Pereira AJ, Akhmanova A, Maiato H (2013) Aurora B spatially regulates EB3 phosphorylation to coordinate daughter cell adhesion with cytokinesis. J Cell Biol 201:709–724. doi:10.1083/jcb.201301131

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  50. Iimori M, Watanabe S, Kiyonari S et al (2016) Phosphorylation of EB2 by Aurora B and CDK1 ensures mitotic progression and genome stability. Nat Commun 7:11117. doi:10.1038/ncomms11117

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  51. Sun L, Gao J, Dong X, et al (2008) EB1 promotes Aurora-B kinase activity through blocking its inactivation by protein phosphatase 2 A. Proc Natl Acad Sci 105:7153–7158. doi:10.1073/pnas.0710018105

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  52. Le Grand M, Rovini A, Bourgarel-Rey V et al (2014) ROS-mediated EB1 phosphorylation through Akt/GSK3β pathway: implication in cancer cell response to microtubule-targeting agents. Oncotarget 5:3408–3423. doi:10.18632/oncotarget.1982

    Article  PubMed  Google Scholar 

  53. Luo Y, Ran J, Xie S et al (2016) ASK1 controls spindle orientation and positioning by phosphorylating EB1 and stabilizing astral microtubules. Cell Discov 2:16033. doi:10.1038/celldisc.2016.33

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  54. Ran J, Luo Y, Zhang Y et al (2016) Phosphorylation of EB1 regulates the recruitment of CLIP-170 and p150glued to the plus ends of astral microtubules. Oncotarget. doi:10.18632/oncotarget.14222

    Google Scholar 

  55. Zhang Y, Luo Y, Lyu R, et al (2016) Proto-oncogenic Src phosphorylates EB1 to regulate the microtubule-focal adhesion crosstalk and stimulate cell migration. Theranostics 6:2129–2140. doi:10.7150/thno.16356

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  56. Stenner F, Liewen H, Göttig S et al (2013) RP1 is a phosphorylation target of CK2 and is involved in cell adhesion. PloS One 8:e67595. doi:10.1371/journal.pone.0067595

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  57. Komarova YA, Huang F, Geyer M et al (2012) VE-cadherin signaling induces EB3 phosphorylation to suppress microtubule growth and assemble adherens junctions. Mol Cell 48:914–925. doi:10.1016/j.molcel.2012.10.011

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  58. Chen J, Luo Y, Li L et al (2014) Phosphoregulation of the dimerization and functions of end-binding protein 1. Protein Cell 5:795–799. doi:10.1007/s13238-014-0081-9

    Article  PubMed  PubMed Central  Google Scholar 

  59. Xia P, Wang Z, Liu X, et al (2012) EB1 acetylation by P300/CBP-associated factor (PCAF) ensures accurate kinetochore-microtubule interactions in mitosis. Proc Natl Acad Sci 109:16564–16569. doi:10.1073/pnas.1202639109

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  60. Ward T, Wang M, Liu X et al (2013) Regulation of a dynamic interaction between two microtubule-binding proteins, EB1 and TIP150, by the mitotic p300/CBP-associated factor (PCAF) orchestrates kinetochore microtubule plasticity and chromosome stability during mitosis. J Biol Chem 288:15771–15785. doi:10.1074/jbc.M112.448886

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  61. Zhang L, Shao H, Zhu T et al (2013) DDA3 associates with microtubule plus ends and orchestrates microtubule dynamics and directional cell migration. Sci Rep 3:1681. doi:10.1038/srep01681

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  62. Rovini A, Gauthier G, Bergès R et al (2013) Anti-migratory effect of vinflunine in endothelial and glioblastoma cells is associated with changes in EB1 C-terminal detyrosinated/tyrosinated status. PLoS One 8:e65694. doi:10.1371/journal.pone.0065694

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  63. Jordan MA, Wilson L (2004) Microtubules as a target for anticancer drugs. Nat Rev Cancer 4:253–265. doi:10.1038/nrc1317

    CAS  Article  PubMed  Google Scholar 

  64. Dumontet C, Jordan MA (2010) Microtubule-binding agents: a dynamic field of cancer therapeutics. Nat Rev Drug Discov 9:790–803. doi:10.1038/nrd3253

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  65. Doodhi H, Prota AE, Rodríguez-García R et al (2016) Termination of protofilament elongation by eribulin induces lattice defects that promote microtubule catastrophes. Curr Biol 26:1713–1721. doi:10.1016/j.cub.2016.04.053

    CAS  Article  PubMed  Google Scholar 

  66. Smith JA, Wilson L, Azarenko O et al (2010) Eribulin binds at microtubule ends to a single site on tubulin to suppress dynamic instability. BioChemistry 49:1331–1337. doi:10.1021/bi901810u

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  67. Nogales E, Wolf SG, Khan IA et al (1995) Structure of tubulin at 6.5 Å and location of the taxol-binding site. Nature 375:424–427. doi:10.1038/375424a0

    CAS  Article  PubMed  Google Scholar 

  68. Pourroy B, Honore S, Pasquier E et al (2006) Antiangiogenic concentrations of vinflunine increase the interphase microtubule dynamics and decrease the motility of endothelial cells. Cancer Res 66:3256–3263. doi:10.1158/0008-5472.CAN-05-3885

    CAS  Article  PubMed  Google Scholar 

  69. Pagano A, Honoré S, Mohan R et al (2012) Epothilone B inhibits migration of glioblastoma cells by inducing microtubule catastrophes and affecting EB1 accumulation at microtubule plus ends. Biochem Pharmacol 84:432–443. doi:10.1016/j.bcp.2012.05.010

    CAS  Article  PubMed  Google Scholar 

  70. O’Rourke B, Yang C-PH, Sharp D, Horwitz SB (2014) Eribulin disrupts EB1-microtubule plus-tip complex formation. Cell Cycle 13:3218–3221. doi:10.4161/15384101.2014.950143

    Article  PubMed  PubMed Central  Google Scholar 

  71. Chiu C-T, Liao C-K, Shen C-C et al (2015) HYS-32-Induced Microtubule Catastrophes in Rat Astrocytes Involves the PI3K-GSK3beta Signaling Pathway. PLoS One 10:e0126217. doi:10.1371/journal.pone.0126217

    Article  PubMed  PubMed Central  Google Scholar 

  72. Berges R, Baeza-Kallee N, Tabouret E et al (2014) End-binding 1 protein overexpression correlates with glioblastoma progression and sensitizes to Vinca-alkaloids in vitro and in vivo. Oncotarget 5:12769–12787. doi:10.18632/oncotarget.2646

    Article  PubMed  PubMed Central  Google Scholar 

  73. Berges R, Tchoghandjian A, Honore S et al (2016) The novel tubulin-binding, checkpoint activator BAL101553 inhibits EB1-dependent migration and invasion and promotes differentiation of glioblastoma stem-like cells. Mol Cancer Ther 15:2740–2749. doi:10.1158/1535-7163.MCT-16-0252

    CAS  Article  PubMed  Google Scholar 

  74. Luo Y, Li D, Ran J et al (2014) End-binding protein 1 stimulates paclitaxel sensitivity in breast cancer by promoting its actions toward microtubule assembly and stability. Protein Cell 5:469–479. doi:10.1007/s13238-014-0053-0

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  75. Thomas G, Sreeja J, Gireesh K et al (2014) +TIP EB1 downregulates paclitaxel-induced proliferation inhibition and apoptosis in breast cancer cells through inhibition of paclitaxel binding on microtubules. Int J Oncol 46:133–146. doi:10.3892/ijo.2014.2701

    PubMed  Google Scholar 

  76. Tymanskyj SR, Scales TME, Gordon-Weeks PR (2012) MAP1B enhances microtubule assembly rates and axon extension rates in developing neurons. Mol Cell Neurosci 49:110–119. doi:10.1016/j.mcn.2011.10.003

    CAS  Article  PubMed  Google Scholar 

  77. Tortosa E, Galjart N, Avila J, Sayas CL (2013) MAP1B regulates microtubule dynamics by sequestering EB1/3 in the cytosol of developing neuronal cells. EMBO J 32:1293–1306. doi:10.1038/emboj.2013.76

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  78. Sayas CL, Tortosa E, Bollati F et al (2015) Tau regulates the localization and function of End-binding proteins 1 and 3 in developing neuronal cells. J Neurochem 133:653–667. doi:10.1111/jnc.13091

    CAS  Article  PubMed  Google Scholar 

  79. Ramirez-Rios S, Denarier E, Prezel E et al (2016) Tau antagonizes end-binding protein tracking at microtubule ends through a phosphorylation-dependent mechanism. Mol Biol Cell 27:2924–2934. doi:10.1091/mbc.E16-01-0029

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  80. Sayas CL, Avila J (2014) Regulation of EB1/3 proteins by classical MAPs in neurons. Bioarchitecture 4:1–5. doi:10.4161/bioa.27774

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  81. Avila J, Pallas N, Bolós M et al (2016) Intracellular and extracellular microtubule associated protein tau as a therapeutic target in Alzheimer disease and other tauopathies. Expert Opin Ther Targets 20:653–661. doi:10.1517/14728222.2016.1131269

    CAS  Article  PubMed  Google Scholar 

  82. Kapitein LC, Yau KW, Gouveia SM et al (2011) NMDA receptor activation suppresses microtubule growth and spine entry. J Neurosci 31:8194–8209. doi:10.1523/JNEUROSCI.6215-10.2011

    CAS  Article  PubMed  Google Scholar 

  83. Velot L, Molina A, Rodrigues-Ferreira S et al (2015) Negative regulation of EB1 turnover at microtubule plus ends by interaction with microtubule-associated protein ATIP3. Oncotarget 6:43557–43570. doi:10.18632/oncotarget.6196

    PubMed  PubMed Central  Google Scholar 

  84. Rodrigues-Ferreira S, Di Tommaso A, Dimitrov A et al (2009) 8p22 MTUS1 gene product ATIP3 is a novel anti-mitotic protein underexpressed in invasive breast carcinoma of poor prognosis. PLoS One 4:e7239. doi:10.1371/journal.pone.0007239

    Article  PubMed  PubMed Central  Google Scholar 

  85. Rodrigues-Ferreira S, Nahmias C (2010) An ATIPical family of angiotensin II AT2 receptor-interacting proteins. Trends Endocrinol Metab 21:684–690. doi:10.1016/j.tem.2010.08.009

    CAS  Article  PubMed  Google Scholar 

  86. Molina A, Rodrigues-Ferreira S, Di Tommaso A, Nahmias C (2011) ATIP, a novel superfamily of microtubule-associated proteins. Med/Sci (Paris) 27:244–246. doi:10.1051/medsci/2011273244

    Article  Google Scholar 

  87. Molina A, Velot L, Ghouinem L et al (2013) ATIP3, a novel prognostic marker of breast cancer patient survival, limits cancer cell migration and slows metastatic progression by regulating microtubule dynamics. Cancer Res 73:2905–2915. doi:10.1158/0008-5472.CAN-12-3565

    CAS  Article  PubMed  Google Scholar 

  88. Orimo T, Ojima H, Hiraoka N et al (2008) Proteomic profiling reveals the prognostic value of adenomatous polyposis coli-end-binding protein 1 in hepatocellular carcinoma. Hepatology 48:1851–1863. doi:10.1002/hep.22552

    CAS  Article  PubMed  Google Scholar 

  89. Dong X, Liu F, Sun L et al (2010) Oncogenic function of microtubule end-binding protein 1 in breast cancer. J Pathol 220:361–369. doi:10.1002/path.2662

    CAS  PubMed  Google Scholar 

  90. Sugihara Y, Taniguchi H, Kushima R et al (2012) Proteomic-based identification of the APC-binding protein EB1 as a candidate of novel tissue biomarker and therapeutic target for colorectal cancer. J Proteomics 75:5342–5355. doi:10.1016/j.jprot.2012.06.013

    CAS  Article  PubMed  Google Scholar 

  91. Stypula-Cyrus Y, Mutyal NN, Dela Cruz M et al (2014) End-binding protein 1 (EB1) up-regulation is an early event in colorectal carcinogenesis. FEBS Lett 588:829–835. doi:10.1016/j.febslet.2014.01.046

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  92. Kumar M, Mehra S, Thakar A et al (2016) End Binding 1 (EB1) overexpression in oral lesions and cancer: a biomarker of tumor progression and poor prognosis. Clin Chim Acta 459:45–52. doi:10.1016/j.cca.2016.05.012

    CAS  Article  PubMed  Google Scholar 

  93. Le niewska K, Warbrick E, Ohkura H (2014) Peptide aptamers define distinct EB1- and EB3-binding motifs and interfere with microtubule dynamics. Mol Biol Cell 25:1025–1036. doi:10.1091/mbc.E13-08-0504

    Article  Google Scholar 

  94. van de Willige D, Hoogenraad CC, Akhmanova A (2016) Microtubule plus-end tracking proteins in neuronal development. Cell Mol Life Sci 73:2053–2077. doi:10.1007/s00018-016-2168-3

    Article  PubMed  PubMed Central  Google Scholar 

  95. Watanabe T, Kakeno M, Matsui T et al (2015) TTBK2 with EB1/3 regulates microtubule dynamics in migrating cells through KIF2A phosphorylation. J Cell Biol 210:737–751. doi:10.1083/jcb.201412075

    CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references

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.

Author information

Author notes

  1. Angie Molina

    Present address: CBD, University of Toulouse-3, Toulouse, France

Affiliations

  1. Inserm U981, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94800, Villejuif, France

    Anne Nehlig, Angie Molina, Sylvie Rodrigues-Ferreira & Clara Nahmias

  2. University Paris Saclay, 94800, Villejuif, France

    Anne Nehlig, Angie Molina, Sylvie Rodrigues-Ferreira & Clara Nahmias

  3. Aix Marseille University, Inserm U-911, CRO2, Marseille, France

    Stéphane Honoré

  4. Service Pharmacie, CHU Hôpital de La Timone, APHM, Marseille, France

    Stéphane Honoré

Authors
  1. Anne Nehlig
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Angie Molina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sylvie Rodrigues-Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stéphane Honoré
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Clara Nahmias
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Clara Nahmias.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-017-2476-2

Keywords

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