Mechanism, Function and Regulation of Microtubule-Dependent Microtubule Amplification in Mitosis

  • Zhu, Hui (Department of Biological Sciences, Stanford University) ;
  • Fang, Kayleen (Department of Biological Sciences, Stanford University) ;
  • Fang, Guowei (Department of Biological Sciences, Stanford University)
  • Received : 2008.12.03
  • Accepted : 2008.12.07
  • Published : 2009.01.31


Mitotic spindle mediates the segregation of chromosomes in the cell cycle and the proper function of the spindle is crucial to the high fidelity of chromosome segregation and to the stability of the genome. Nucleation of microtubules (MTs) from centrosomes and chromatin represents two well-characterized pathways essential for the assembly of a dynamic spindle in mitosis. Recently, we identified a third MT nucleation pathway, in which existing MTs in the spindle act as a template to promote the nucleation and polymerization of MTs, thereby efficiently amplifying MTs in the spindle. We will review here our current understanding on the molecular mechanism, the physiological function and the cell-cycle regulation of MT amplification.


Supported by : National Institutes of Health


  1. Kline-Smith, S.L., and Walczak, C.E. (2004). Mitotic spindle assembly and chromosome segregation: refocusing on microtubule dynamics. Mol. Cell 15, 317-327
  2. Murata, T., Sonobe, S., Baskin, T.I., Hyodo, S., Hasezawa, S., Nagata, T., Horio, T., and Hasebe, M. (2005). Microtubuledependent microtubule nucleation based on recruitment of $\gamma$-tubulin in higher plants. Nat. Cell Biol. 7, 961-968
  3. Petronczki, M., Lenart, P., and Peters, J.M. (2008). Polo on the Rise-from Mitotic Entry to Cytokinesis with Plk1. Dev. Cell 14, 646-659
  4. McIntosh, J.R., Grishchuk, E.L., and West, R.R. (2002). Chromosome-microtubule interactions during mitosis. Annu. Rev. Cell Dev. Biol. 18, 193-219
  5. Zhu, H., Coppinger, J.A., Jang, C.Y., Yates, J.R., 3rd, and Fang, G. (2008). FAM29A promotes microtubule amplification via recruitment of the NEDD1–$\gamma$-tubulin complex to the mitotic spindle. J. Cell Biol. 183, 835-848
  6. Kirschner, M., and Mitchison, T. (1986). Beyond self-assembly: from microtubules to morphogenesis. Cell 45, 329-342
  7. Maiato, H., DeLuca, J., Salmon, E.D., and Earnshaw, W.C. (2004). The dynamic kinetochore-microtubule interface. J. Cell Sci. 117, 5461-5477
  8. Luders, J., Patel, U.K., and Stearns, T. (2006). GCP-WD is a $\gamma$-tubulin targeting factor required for centrosomal and chromatin-mediated microtubule nucleation. Nat. Cell Biol. 8, 137-147
  9. Barr, F.A., Sillje, H.H., and Nigg, E.A. (2004). Polo-like kinases and the orchestration of cell division. Nat. Rev. Mol. Cell Biol. 5, 429-440
  10. Goshima, G., Mayer, M., Zhang, N., Stuurman, N., and Vale, R.D. (2008). Augmin: a protein complex required for centrosomeindependent microtubule generation within the spindle. J. Cell Biol. 181, 421-429
  11. van de Weerdt, B.C., and Medema, R.H. (2006). Polo-like kinases: a team in control of the division. Cell Cycle 5, 853-864
  12. Wiese, C., and Zheng, Y. (2006). Microtubule nucleation: $\gamma$-tubulin and beyond. J. Cell Sci.119, 4143-4153
  13. Scholey, J.M., Brust-Mascher, I., and Mogilner, A. (2003). Cell division. Nature 422, 746-752
  14. Gadde, S., and Heald, R. (2004). Mechanisms and molecules of the mitotic spindle. Curr. Biol. 14, R797-805
  15. Haren, L., Remy, M.H., Bazin, I., Callebaut, I., Wright, M., and Merdes, A. (2006). NEDD1-dependent recruitment of the $\gamma$-tubulin ring complex to the centrosome is necessary for centriole duplication and spindle assembly. J. Cell Biol. 175, 505-515
  16. Janson, M.E., Setty, T.G., Paoletti, A., and Tran, P.T. (2005). Efficient formation of bipolar microtubule bundles requires microtubule-bound $\gamma$-tubulin complexes. J. Cell Biol. 169, 297-308