The Evolution of Microtubule End-Binding Protein 1 (EB1) and Roles in Regulating Microtubule Behavior


All organisms must transmit genetic information to offspring through cell division, and mitotic spindle participates in the process. Spindle dynamics through depolymerization or polymerization of microtubules generates the driving force required for chromosome movements in mitosis. To date, studies have shown that microtubule arrays control the directions of cell division and diverse microtubule-associated proteins regulate cell division. But a clear picture of how microtubules and microtubule-associated proteins modulate cell division remains unknown. Depletion of end-binding protein 1 by RNA-mediated inhibition shows that one of the microtubule-associated proteins, end-binding protein 1, plays a crucial role in mitotic spindle formation and promotes microtubule dynamics and is needed for the proper segregation of mitotic chromosomes during anaphase in Drosophila cells. Here, we review the properties of end-binding protein 1 and the roles of end-binding protein 1 in regulating microtubule behavior and in cell cycle.

Share and Cite:

Liu, J. and Han, R. (2015) The Evolution of Microtubule End-Binding Protein 1 (EB1) and Roles in Regulating Microtubule Behavior. American Journal of Plant Sciences, 6, 2114-2121. doi: 10.4236/ajps.2015.613212.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Schuyler, S.C. and Pellman, D. (2001) Microtubule “Plus-End-Tracking Proteins”: The End Is Just the Beginning. Cell, 105, 421-424.
[2] Akhmanova, A. and Steinmetz, M.O. (2008) Tracking the Ends: A Dynamic Protein Network Controls the Fate of Microtubule Tips. Nature Reviews Molecular Cell Biology, 9, 309-322.
[3] Akhmanova, A. and Hoogenraad, C.C. (2005) Microtubule Plus-End-Tracking Proteins: Mechanisms and Functions. Current Opinion in Cell Biology, 17, 47-54.
[4] Honnappa, S., Gouveia, S.M., Weisbrich, A., Damberger, F.F., Bhavesh, N.S., Jawhari, H., Grigoriev, I., van Rijssel, F.J.A., Buey, R.M., Lawera, A., Jelesarov, I., Winkler, F.K., Wüthrich, K., Akhmanova, A. and Steinmetz, M.O. (2009) An EB1-Binding Motif Acts as a Microtubule Tip Localization Signal. Cell, 138, 366-376.
[5] Slep, K.C. (2010) Structural and Mechanistic Insights into Microtubule End-Binding Proteins. Current Opinion in Cell Biology, 22, 88-95.
[6] Lansbergen, G. and Akhmanova, A. (2006) Microtubule Plus End: A Hub of Cellular Activities. Traffic, 7, 499-507.
[7] Vaughan, K.T. (2005) TIP Maker and TIP Marker; EB1 as a Master Controller of Microtubule Plus Ends. The Journal of Cell Biology, 171, 197-200.
[8] Piehl, M. and Cassimeris, L. (2003) Organization and Dynamics of Growing Microtubule Plus Ends during Early Mitosis. Molecular Biology of the Cell, 14, 916-925.
[9] Cheerambathur, D.K. and Desai, A. (2014) Linked in: Formation and Regulation of Microtubule Attachments during Chromosome Segregation. Current Opinion in Cell Biology, 26, 113-122.
[10] Zhai, Y., Kronebusch, P.J., Simon, P.M. and Borisy, G.G. (1996) Microtubule Dynamics at the G2/M Transition: Abrupt Breakdown of Cytoplasmic Microtubules at Nuclear Envelope Breakdown and Implications for Spindle Morphogenesis. The Journal of Cell Biology, 135, 201-214.
[11] Komaki1, S., Abe, T., Coutuer, S., Inzé, D., Russinova, E. and Hashimoto, T. (2010) Nuclear-Localized Subtype of End-Binding 1 Protein Regulates Spindle Organization in Arabidopsis. Journal of Cell Science, 123, 451-459.
[12] Rogers, S.L., Rogers, G.C., Sharp, D.J. and Vale, R.D. (2002) Drosophila EB1 Is Important for Proper Assembly, Dynamics, and Positioning of the Mitotic Spindle. The Journal of Cell Biology, 158, 873-884.
[13] Green, R.A., Wollman, R. and Kaplan, K.B. (2005) APC and EB1 Function Together in Mitosis to Regulate Spindle Dynamics and Chromosome Alignment. Molecular Biology of the Cell, 16, 4609-4622.
[14] Cassirneris, L. (1993) Regulation of Microtubule Dynamic Instability. Cell Motility and the Cytoskeleton, 26, 275-281.
[15] Howard, J. and Hyman, A.A. (2009) Growth, Fluctuation and Switching at Microtubule plus Ends. Nature Reviews Molecular Cell Biology, 10, 569-574.
[16] Jiang, K. and Akhmanova, A. (2011) Microtubule Tip-Interacting Proteins: A View from Both Ends. Current Opinion in Cell Biology, 23, 94-101.
[17] Mitchison, T. and Kirschner, M. (1984) Dynamic Instability of Microtubule Growth. Nature, 312, 237-242.
[18] Masoud, K., Herzog, E., Chaboute, M.E. and Schmit, A.C. (2013) Microtubule Nucleation and Establishment of the Mitotic Spindle in Vascular Plant Cells. The Plant Journal, 75, 245-257.
[19] Howard, J. and Hyman, A.A. (2003) Dynamics and Mechanics of the Microtubule plus End. Nature, 422, 753-758.
[20] Maurer, S.P., Cade, N.I., Bohner, G., Gustafsson, N., Boutant, E. and Surrey, T. (2014) EB1 Accelerates Two Conformational Transitions Important for Microtubule Maturation and Dynamics. Current Biology, 24, 372-384.
[21] Su, L.K., Burrell, M., Hill, D.E., Gyuris, J., Brent, R., Wiltshire, R., Trent, J., Vogelstein, B. and Kinzler, K.W. (1995) APC Binds to the Novel Protein EB1. Cancer Research, 55, 2972-2977.
[22] Hayashi, I. and Ikura, M. (2003) Crystal Structure of the Amino-Terminal Microtubule-Binding Domain of End-Binding Protein 1 (EB1). The Journal of Biological Chemistry, 278, 36430-36434.
[23] Komarova, Y., De Groot, C.O., Grigoriev, I., Gouveia, S.M., Munteanu, E.L., Schober, J.M., Honnappa, S., Buey, R.M., Hoogenraad, C.C., Dogterom, M., Borisy, G.G., Steinmetz, M.O. and Akhmanova, A. (2009) Mammalian End Binding Proteins Control Persistent Microtubule Growth. The Journal of Cell Biology, 184, 691-706.
[24] Steinmetz, M.O. and Akhmanova, A. (2008) Capturing Protein Tails by CAP-Gly Domains. Trends in Biochemical Sciences, 33, 535-545.
[25] Galjart, N. (2010) Plus-End-Tracking Proteins and Their Interactions at Microtubule Ends. Current Biology, 20, 528-537.
[26] Kumar, P. and Wittmann, T. (2012) +TIPs: SxIPping along Microtubule Ends. Trends in Cell Biology, 22, 418-428.
[27] Maurer, S.P., Fourniol, F.J., Bohner, G., Moores, C.A. and Surrey, T. (2012) EBs Recognize a Nucleotide-Dependent Structural Cap at Growing Microtubule Ends. Cell, 149, 371-382.
[28] Su, L.K. and Qi, Y. (2001) Characterization of Human MAPRE Genes and Their Proteins. Genomics, 71, 142-149.
[29] Straube, A. and Merdes, A. (2007) EB3 Regulates Microtubule Dynamics at the Cell Cortex and Is Required for Myoblast Elongation and Fusion. Current Biology, 17, 1318-1325.
[30] Bisgrove, S.R., Hable, W.E. and Kropf, D.L. (2004) +TIPs and Microtubule Regulation. The Beginning of the Plus End in Plants. Plant Physiology, 136, 3855-3863.
[31] Guo, L., Ho, C.M., Kong, Z., Lee, Y.R., Qian, Q. and Liu, B. (2009) Evaluating the Microtubule Cytoskeleton and Its Interacting Proteins in Monocots by Mining the Rice Genome. Annals of Botany, 103, 387-402.
[32] Chan, J., Calder, G.M., Doonan, J.H. and Lloyd, C.W. (2003) EB1 Reveals Mobile Microtubule Nucleation Sites in Arabidopsis. Nature Cell Biology, 5, 967-971.
[33] Chan, J., Calder, G., Fox, S. and Lloyd, C. (2005) Localization of the Microtubule End Binding Protein EB1 Reveals Alternative Pathways of Spindle Development in Arabidopsis Suspension Cells. Plant Cell, 17, 1737-1748.
[34] Van Damme, D., Bouget, F.Y., Van Poucke, K., Inze, D. and Geelen, D. (2004) Molecular Dissection of Plant Cytokinesis and Phragmoplast Structure: A Survey of GFP-Tagged Proteins. The Plant Journal, 40, 386-398.
[35] Berrueta, L., Kraeft, S.K., Tirnauer, J.S., Schuyler, S.C., Chen, L.B., Hill, D.E., Pellman, D. and Bierer, B.E. (1998) The Adenomatous Polyposis Coli-Binding Protein EB1 Is Associated with Cytoplasmic and Spindle Microtubules. Cell Biology, 95, 10596-10601.
[36] Tirnauer, J.S., Canman, J.C., Salmon, E.D. and Mitchison, T.J. (2002) EB1 Targets to Kinetochores with Attached, Polymerizing Microtubules. Molecular Biology of the Cell, 13, 4308-4316.
[37] Akhmanova, A. and Steinmetz, M.O. (2010) Microtubule +TIPs at a Glance. Journal of Cell Science, 123, 3415-3419.
[38] Gard, D.L. and Kirschner, M.W. (1987) A Microtubule-Associated Protein from Xenopus Eggs That Specifically Promotes Assembly at the Plus-End. The Journal of Cell Biology, 105, 2203-2215.
[39] Bieling, P., Kandels-Lewis, S., Telley, I.A., van Dijk, J., Janke, C. and Surrey, T. (2008) CLIP-170 Tracks Growing Microtubule Ends by Dynamically Recognizing Composite EB1/Tubulin-Binding Sites. The Journal of Cell Biology, 183, 1223-1233.
[40] Bu, W. and Su, L.K. (2001) Regulation of Microtubule Assembly by Human EB1 Family Proteins. Nature, 20, 3185-3192.
[41] Tirnauer, J.S. and Bierer, B.E. (2000) EB1 Proteins Regulate Microtubule Dynamics, Cell Polarity, and Chromosome Stability. The Journal of Cell Biology, 149, 761-766.
[42] Beinhauer, J.D., Hagan, I.M., Hegemann, J.H. and Fleig, U. (1997) Mal3, the Fission Yeast Homologue of the Human APC-Interacting Protein EB-1 Is Required for Microtubule Integrity and the Maintenance of Cell Form. The Journal of Cell Biology, 139, 717-728.
[43] Berrueta, L., Tirnauer, J.S., Schuyler, S.C., Pellman, D. and Bierer, B.E. (1999) The APC-Associated Protein EB1 Associates with Components of the Dynactin Complex and Cytoplasmic Dynein Intermediate Chain. Current Biology, 9, 425-428.
[44] Maurera, S.P., Bieling, P., Cope, J., Hoenger, A. and Surrey, T. (2011) GTPγS Microtubules Mimic the Growing Microtubule End Structure Recognized by End-Binding Proteins (EBs). Proceedings of the National Academy of Sciences of the United States of America, 108, 3988-3993.
[45] Bieling, P., Laan, L., Schek, H., Munteanu, E.L., Sandblad, L., Dogterom, M., Brunner, D. and Surrey, T. (2007) Reconstitution of a Microtubule Plus-End Tracking System in Vitro. Nature, 450, 1100-1105.
[46] Ligon, L.A., Shelly, S.S., Tokito, M. and Holzbaur, E.L. (2003) The Microtubule Plus-End Proteins EB1 and Dynactin Have Differential Effects on Microtubule Polymerization. Molecular Biology of the Cell, 14, 1405-1417.
[47] Lopus, M., Manatschal, C., Buey, R.M., Bjelic, S., Miller, H.P., Steinmetz, M.O. and Wilson, L. (2012) Cooperative Stabilization of Microtubule Dynamics by EB1 and CLIP-170 Involves Displacement of Stably Bound P(i) at Microtubule Ends. Biochemistry, 51, 3021-3030.
[48] Mimori-Kiyosue, Y., Grigoriev, I., Lansbergen, G., Sasaki, H., Matsui, C., Severin, F., Galjart, N., Grosveld, F., Vorobjev, I., Tsukita, S. and Akhmanova, A. (2005) CLASP1 and CLASP2 Bind to EB1 and Regulate Microtubule Plus-End Dynamics at the Cell Cortex. The Journal of Cell Biology, 168, 141-153.
[49] Montenegro Gouveia, S., Leslie, K., Kapitein, L.C., Buey, R.M., Grigoriev, I., Wagenbach, M., Smal, I., Meijering, E., Hoogenraad, C.C., Wordeman, L., Steinmetz, M.O. and Akhmanova, A. (2010) In Vitro Reconstitution of the Functional Interplay between MCAK and EB3 at Microtubule Plus Ends. Current Biology, 20, 1717-1722.
[50] Zimniak, T., Stengl, K., Mechtler, K. and Westermann, S. (2009) Phospho-Regulation of the Budding Yeast EB1 Homologue Bim1p by Aurora/Ipl1p. The Journal of Cell Biology, 186, 379-391.
[51] Iimori, M., Ozaki, K., Chikashige, Y., Habu, T., Hiraoka, Y., Maki, T., Hayashi, I., Obuse, C. and Matsumoto, T. (2012) A Mutation of the Fission Yeast EB1 Overcomes Negative Regulation by Phosphorylation and Stabilizes Microtubules. Experimental Cell Research, 318, 262-275.
[52] Ban, R., Matsuzaki, H., Akashi, T., Sakashita, G., Taniguchi, H., Park, S.Y., Tanaka, H., Furukawa, K. and Urano, T. (2009) Mitotic Regulation of the Stability of Microtubule Plus-End Tracking Protein EB3 by Ubiquitin Ligase SIAH-1 and Aurora Mitotic Kinases. The Journal of Biological Chemistry, 284, 8367-8381.
[53] Ferreira, J.G., Pereira, A.J., Akhmanova, A. and Maiato, H. (2013) Aurora B Spatially Regulates EB3 Phosphorylation to Coordinate Daughter Cell Adhesion with Cytokinesis. The Journal of Cell Biology, 201, 709-724.
[54] Komarova, Y.A., Huang, F., Geyer, M., Daneshjou, N., Garcia, A., Idalino, L., Kreutz, B., Mehta, D. and Malik, A.B. (2012) VE-Cadherin Signaling Induces EB3 Phosphorylation to Suppress Microtubule Growth and Assemble Adherens Junctions. Molecular Cell, 48, 914-925.
[55] Gadde, S. and Heald, R. (2004) Mechanisms and Molecules of the Mitotic Spindle. Current Biology, 14, 797-805.
[56] vander Vaart, B., Akhmanova, A. and Straube, A. (2009) Regulation of Microtubule Dynamic Instability. Biochemical Society Transactions, 37, 1007-1013.
[57] Zhai, Y., Kronebusch, P.J., Simon, P.M. and Borisy, G.G. (1996) Microtubule Dynamics at the G2/M Transition: Abrupt Breakdown of Cytoplasmic Microtubules at Nuclear Envelope Breakdown and Implications for Spindle Morphogenesis. The Journal of Cell Biology, 135, 201-214.
[58] Schuyler, S.C. and Pellman, D. (2001) Search, Capture and Signal: Games Microtubules and Centrosomes Play. Journal of Cell Science, 114, 247-255.
[59] Kronja, I., Kruljac-Letunic, A., Caudron-Herger, M., Bieling, P. and Karsenti, E. (2009) XMAP215-EB1 Interaction Is Required for Proper Spindle Assembly and Chromosome Segregation in Xenopus Egg Extract. Molecular Biology of the Cell, 20, 2684-2696.
[60] Han, R., Wang, X., Yue, M. and Qi, Z. (2002) Effects of the Enhanced UV-B Radiation on the Body Cell Mitosis of the Wheat. Acta Genetica Sinica, 29, 537-541.
[61] Aihua, G., Limei, G., Yongfeng, L. and Han, R. (2010) Influence on Microtubule in Wheat Mesophyll Cell Exposed to Enhanced Ultraviolet-B Radiation and He-Ne Laser Irradiation. Guihaia, 30, 250-255.
[62] Bisgrove, S.R., Lee, Y.R., Liu, B., Peters, N.T. and Kropf, D.L. (2008) The Microtubule Plus-End Binding Protein EB1 Functions in Root Responses to Touch and Gravity Signals in Arabidopsis. Plant Cell, 20, 396-410.
[63] Squires, S. and Bisgrove, S. (2013) The Microtubule-Associated Protein END BINDING1b, Auxin, and Root Responses to Mechanical Cues. Journal of Plant Growth Regulation, 32, 681-691.

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.