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Mitotic spindle assembly in animal cells: a fine balancing act

Key Points

  • The assembly of a bipolar microtubule-based spindle is crucial for the accurate and timely segregation of the chromosomes into the two daughter cells during mitosis.

  • Three microtubule nucleation pathways function in mitotic cells to contribute microtubules to the assembling spindle, namely the centrosome-, chromatin- and microtubule-mediated pathways.

  • Microtubules nucleated from the centrosomes find the chromosomes via 'search and capture' — a process that relies on the dynamic instability of microtubules — which allows them to search space to contact the chromosomes. When a microtubule contacts a kinetochore, it is captured and becomes stabilized to form kinetochore fibres (K-fibres).

  • The speed and efficiency of chromosome capture is promoted by the chromatin-mediated pathway that biases microtubule nucleation and stabilization to the vicinity of the chromosomes.

  • Microtubules are also generated from within the spindle itself via Augmin, which promotes microtubule nucleation from pre-existing microtubules. This nucleation increases the density of microtubules within the spindle and thus contributes to its robustness.

  • Although the nucleation pathways are at least partially redundant, they are integrated to provide an intricate balance of microtubule nucleation that ensures the fidelity of chromosome segregation and the timely completion of mitosis. In the absence of any one of the pathways, spindle assembly still occurs — although with increased use of the remaining pathways — but mitosis takes longer and this can result in genome instability.

Abstract

The mitotic spindle has a crucial role in ensuring the accurate segregation of chromosomes into the two daughter cells during cell division, which is paramount for maintaining genome integrity. It is a self-organized and dynamic macromolecular structure that is constructed from microtubules, microtubule-associated proteins and motor proteins. Thirty years of research have led to the identification of centrosome-, chromatin- and microtubule-mediated microtubule nucleation pathways that each contribute to mitotic spindle assembly. Far from being redundant pathways, data are now emerging regarding how they function together to ensure the timely completion of mitosis. We are also beginning to comprehend the multiple mechanisms by which cells regulate spindle scaling. Together, this research has increased our understanding of how cells coordinate hundreds of proteins to assemble the dynamic, precise and robust structure that is the mitotic spindle.

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Figure 1: Overview of the mitotic spindle.
Figure 2: Centrosome-mediated microtubule nucleation.
Figure 3: Chromatin-mediated microtubule nucleation.
Figure 4: Microtubule-mediated microtubule nucleation.

References

  1. 1

    Dumont, J. & Desai, A. Acentrosomal spindle assembly and chromosome segregation during oocyte meiosis. Trends Cell Biol. 22, 241–249 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2

    Severson, A. F., Dassow von, G. & Bowerman, B. in Essays on Developmental Biology, Part A Vol. 116 (ed. Wassarman, P. M.) 65–98 (Elsevier, 2016).

    Book  Google Scholar 

  3. 3

    Kollman, J. M., Merdes, A., Mourey, L. & Agard, D. A. Microtubule nucleation by γ-tubulin complexes. Nat. Rev. Mol. Cell Biol. 12, 709–721 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4

    Mitchison, T. & Kirschner, M. Dynamic instability of microtubule growth. Nature 312, 237–242 (1984). In this paper, the authors describe the ability of microtubules to switch between periods of growth and shrinkage, known as dynamic instability, when they lose their GTP caps.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5

    Dumont, S. & Mitchison, T. J. Force and length in the mitotic spindle. Curr. Biol. 19, R749–R761 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6

    Grill, S. W. & Hyman, A. A. Spindle positioning by cortical pulling forces. Dev. Cell 8, 461–465 (2005).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. 7

    McNally, F. J. Mechanisms of spindle positioning. J. Cell Biol. 200, 131–140 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8

    Khodjakov, A., Cole, R. W., Oakley, B. R. & Rieder, C. L. Centrosome-independent mitotic spindle formation in vertebrates. Curr. Biol. 10, 59–67 (2000). The authors use laser ablation of centrosomes to show that they are not required for spindle assembly in somatic cells.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9

    Hayward, D., Metz, J., Pellacani, C. & Wakefield, J. G. Synergy between multiple microtubule-generating pathways confers robustness to centrosome-driven mitotic spindle formation. Dev. Cell 28, 81–93 (2014). This paper demonstrates that there is integration and adaptability between the three microtubule nucleation pathways, and that removal of one pathway leads to an increase in the activity of the others.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10

    Lüders, J., Patel, U. K. & Stearns, T. GCP-WD is a γ-tubulin targeting factor required for centrosomal and chromatin-mediated microtubule nucleation. Nat. Cell Biol. 8, 137–147 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. 11

    Gaglio, T. et al. Opposing motor activities are required for the organization of the mammalian mitotic spindle pole. J. Cell Biol. 135, 399–414 (1996).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12

    Walczak, C. E., Vernos, I., Mitchison, T. J., Karsenti, E. & Heald, R. A model for the proposed roles of different microtubule-based motor proteins in establishing spindle bipolarity. Curr. Biol. 8, 903–913 (1998).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13

    Wilde, A. et al. Ran stimulates spindle assembly by altering microtubule dynamics and the balance of motor activities. Nat. Cell Biol. 3, 221–227 (2001).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14

    Goshima, G. & Vale, R. D. The roles of microtubule-based motor proteins in mitosis. J. Cell Biol. 162, 1003–1016 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15

    Goshima, G., Nédélec, F. & Vale, R. D. Mechanisms for focusing mitotic spindle poles by minus end–directed motor proteins. J. Cell Biol. 171, 229–240 (2005).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. 16

    Chavali, P. L., Peset, I. & Gergely, F. Centrosomes and mitotic spindle poles: a recent liaison? Biochem. Soc. Trans. 43, 13–18 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17

    Tanenbaum, M. E. & Medema, R. H. Mechanisms of centrosome separation and bipolar spindle assembly. Dev. Cell 19, 797–806 (2010).

    CAS  Article  Google Scholar 

  18. 18

    Conduit, P. T., Wainman, A. & Raff, J. W. Centrosome function and assembly in animal cells. Nat. Rev. Mol. Cell Biol. 16, 611–624 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19

    Heald, R. & Khodjakov, A. Thirty years of search and capture: the complex simplicity of mitotic spindle assembly. J. Cell Biol. 211, 1103–1111 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20

    Wollman, R. et al. Efficient chromosome capture requires a bias in the 'search-and-capture' process during mitotic-spindle assembly. Curr. Biol. 15, 828–832 (2005).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21

    Gruss, O. J. The mechanism of spindle assembly: functions of Ran and its target TPX2. J. Cell Biol. 166, 949–955 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22

    Kalab, P. Visualization of a Ran-GTP gradient in interphase and mitotic Xenopus egg extracts. Science 295, 2452–2456 (2002).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23

    Kaláb, P., Pralle, A., Isacoff, E. Y., Heald, R. & Weis, K. Analysis of a RanGTP-regulated gradient in mitotic somatic cells. Nature 440, 697–701 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 24

    Gruss, O. J. et al. Ran induces spindle assembly by reversing the inhibitory effect of importin alpha on TPX2 activity. Cell 104, 83–93 (2001). References 22–24 describe the analysis of the RAN·GTP gradient that is formed around chromatin during mitosis, and how this gradient promotes microtubule growth around the chromosomes.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. 25

    Clarke, P. R. & Zhang, C. Spatial and temporal coordination of mitosis by Ran GTPase. Nat. Rev. Mol. Cell Biol. 9, 464–477 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26

    Kalab, P. & Heald, R. The RanGTP gradient — a GPS for the mitotic spindle. J. Cell Sci. 121, 1577–1586 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. 27

    Forbes, D. J., Travesa, A., Nord, M. S. & Bernis, C. Nuclear transport factors: global regulation of mitosis. Curr. Opin. Cell Biol. 35, 78–90 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. 28

    Kufer, T. A. et al. Human TPX2 is required for targeting Aurora-A kinase to the spindle. J. Cell Biol. 158, 617–623 (2002).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29

    Sardon, T., Peset, I., Petrova, B. & Vernos, I. Dissecting the role of Aurora A during spindle assembly. EMBO J. 27, 2567–2579 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. 30

    Pinyol, R., Scrofani, J. & Vernos, I. The role of NEDD1 phosphorylation by Aurora A in chromosomal microtubule nucleation and spindle function. Curr. Biol. 23, 143–149 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31

    Nemergut, M. E., Mizzen, C. A., Stukenberg, T., Allis, C. D. & Macara, I. G. Chromatin docking and exchange activity enhancement of RCC1 by histones H2A and H2B. Science 292, 1540–1543 (2001).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32

    Zierhut, C., Jenness, C., Kimura, H. & Funabiki, H. Nucleosomal regulation of chromatin composition and nuclear assembly revealed by histone depletion. Nat. Struct. Mol. Biol. 21, 617–625 (2014).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. 33

    Schaner Tooley, C. E. et al. NRMT is an α-N-methyltransferase that methylates RCC1 and retinoblastoma protein. Nature 466, 1125–1128 (2010).

    CAS  Article  Google Scholar 

  34. 34

    Bierbaum, M. & Bastiaens, P. I. H. Cell cycle-dependent binding modes of the Ran Exchange Factor RCC1 to chromatin. Biophys. J. 104, 1642–1651 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35

    Zhang, M. S., Arnaoutov, A. & Dasso, M. RanBP1 governs spindle assembly by defining mitotic Ran-GTP production. Dev. Cell 31, 393–404 (2014).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36

    Guarguaglini, G. et al. Regulated Ran-binding protein 1 activity is required for organization and function of the mitotic spindle in mammalian cells in vivo. Cell Growth Differ. 11, 455–465 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37

    Maresca, T. J. et al. Spindle assembly in the absence of a RanGTP gradient requires localized CPC activity. Curr. Biol. 19, 1210–1215 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  38. 38

    Carmena, M., Wheelock, M., Funabiki, H. & Earnshaw, W. C. The chromosomal passenger complex (CPC): from easy rider to the godfather of mitosis. Nat. Rev. Mol. Cell Biol. 13, 789–803 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39

    Ghenoiu, C., Wheelock, M. S. & Funabiki, H. Autoinhibition and polo-dependent multisite phosphorylation restrict activity of the histone H3 kinase haspin to mitosis. Mol. Cell 52, 734–745 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. 40

    Zhou, L., Tian, X., Zhu, C., Wang, F. & Higgins, J. M. G. Polo-like kinase-1 triggers histone phosphorylation by haspin in mitosis. EMBO Rep. 15, 273–281 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41

    Kelly, A. E. et al. Chromosomal enrichment and activation of the Aurora B pathway are coupled to spatially regulate spindle assembly. Dev. Cell 12, 31–43 (2007).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. 42

    Andrews, P. D. et al. Aurora B regulates MCAK at the mitotic centromere. Dev. Cell 6, 253–268 (2004).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. 43

    Lan, W. et al. Aurora B phosphorylates centromeric MCAK and regulates its localization and microtubule depolymerization activity. Curr. Biol. 14, 273–286 (2004).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. 44

    Sampath, S. C. et al. The chromosomal passenger complex is required for chromatin-induced microtubule stabilization and spindle assembly. Cell 118, 187–202 (2004).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. 45

    Niethammer, P., Bastiaens, P. & Karsenti, E. Stathmin-tubulin interaction gradients in motile and mitotic cells. Science 303, 1862–1866 (2004).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  46. 46

    Tan, L. & Kapoor, T. M. Examining the dynamics of chromosomal passenger complex (CPC)-dependent phosphorylation during cell division. Proc. Natl Acad. Sci. USA 108, 16675–16680 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  47. 47

    Wang, E., Ballister, E. R. & Lampson, M. A. Aurora B dynamics at centromeres create a diffusion-based phosphorylation gradient. J. Cell Biol. 194, 539–549 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. 48

    Tseng, B. S., Tan, L., Kapoor, T. M. & Funabiki, H. Dual detection of chromosomes and microtubules by the chromosomal passenger complex drives spindle assembly. Dev. Cell 18, 903–912 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  49. 49

    Noujaim, M., Bechstedt, S., Wieczorek, M. & Brouhard, G. J. Microtubules accelerate the kinase activity of Aurora-B by a reduction in dimensionality. PLoS ONE 9, e86786–86789 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. 50

    Tulu, U. S., Fagerstrom, C., Ferenz, N. P. & Wadsworth, P. Molecular requirements for kinetochore-associated microtubule formation in mammalian cells. Curr. Biol. 16, 536–541 (2006).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  51. 51

    Khodjakov, A. Minus-end capture of preformed kinetochore fibers contributes to spindle morphogenesis. J. Cell Biol. 160, 671–683 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  52. 52

    Maiato, H., Rieder, C. L. & Khodjakov, A. Kinetochore-driven formation of kinetochore fibers contributes to spindle assembly during animal mitosis. J. Cell Biol. 167, 831–840 (2004).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  53. 53

    Heald, R. et al. Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts. Nature 382, 420–425 (1996). In this classical paper, the authors demonstrate that DNA-coated beads are able to form spindles in the absence of centrosomes in mitotic X. laevis egg extracts.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  54. 54

    Brinkley, B. R. et al. Movement and segregation of kinetochores experimentally detached from mammalian chromosomes. Nature 336, 251–254 (1988).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  55. 55

    O'Connell, C. B., Loncarek, J., Kaláb, P. & Khodjakov, A. Relative contributions of chromatin and kinetochores to mitotic spindle assembly. J. Cell Biol. 187, 43–51 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  56. 56

    Bernis, C. et al. Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration. Mol. Biol. Cell 25, 992–1009 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  57. 57

    Yokoyama, H. et al. The nucleoporin MEL-28 promotes RanGTP-dependent γ-tubulin recruitment and microtubule nucleation in mitotic spindle formation. Nat. Commun. 5, 3270 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. 58

    Meunier, S. & Vernos, I. K-Fibre minus ends are stabilized by a RanGTP-dependent mechanism essential for functional spindle assembly. Nat. Cell Biol. 13, 1406–1414 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  59. 59

    Meunier, S. et al. An epigenetic regulator emerges as microtubule minus-end binding and stabilizing factor in mitosis. Nat. Commun. 6, 7889 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  60. 60

    Lecland, N. et al. Establishment and mitotic characterization of new Drosophila acentriolar cell lines from DSas-4 mutant. Biol. Open 2, 314–323 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  61. 61

    Mahoney, N. M., Goshima, G., Douglass, A. D. & Vale, R. D. Making microtubules and mitotic spindles in cells without functional centrosomes. Curr. Biol. 16, 564–569 (2006).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  62. 62

    Goshima, G. et al. Genes required for mitotic spindle assembly in Drosophila S2 cells. Science 316, 417–421 (2007).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  63. 63

    Goshima, G., Mayer, M., Zhang, N., Stuurman, N. & Vale, R. D. Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle. J. Cell Biol. 181, 421–429 (2008). References 62 and 63 identified the 5-subunit Augmin complex in flies that promotes microtubule nucleation within the spindle.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  64. 64

    Meireles, A. M., Fisher, K. H., Colombié, N., Wakefield, J. G. and Ohkura, H. Wac: a new augmin subunit required for chromosome alignment but not for acentrosomal microtubule assembly in female meiosis. J. Cell Biol. 184, 777–784 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  65. 65

    Wainman, A. et al. A new Augmin subunit, Msd1, demonstrates the importance of mitotic spindle-templated microtubule nucleation in the absence of functioning centrosomes. Genes Dev. 23, 1876–1881 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  66. 66

    Lawo, S. et al. HAUS, the 8-subunit human augmin complex, regulates centrosome and spindle integrity. Curr. Biol. 19, 816–826 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  67. 67

    Uehara, R. et al. The augmin complex plays a critical role in spindle microtubule generation for mitotic progression and cytokinesis in human cells. Proc. Natl Acad. Sci. USA 106, 6998–7003 (2009). References 66 and 67 identified and functionally characterized the human Augmin complex.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  68. 68

    Zhu, H. et al. FAM29A promotes microtubule amplification via recruitment of the NEDD1–γ-tubulin complex to the mitotic spindle. J. Cell Biol. 183, 835–848 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  69. 69

    Wu, G. et al. Hice1, a novel microtubule-associated protein required for maintenance of spindle integrity and chromosomal stability in human cells. Mol. Cell. Biol. 28, 3652–3662 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  70. 70

    Hsia, K.-C. et al. Reconstitution of the augmin complex provides insights into its architecture and function. Nat. Cell Biol. 16, 852–863 (2014).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  71. 71

    Tsai, C. Y. et al. Aurora-A phosphorylates augmin complex component Hice1 protein at an N-terminal serine/threonine cluster to modulate its microtubule binding activity during spindle assembly. J. Biol. Chem. 286, 30097–30106 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  72. 72

    Johmura, Y. et al. Regulation of microtubule-based microtubule nucleation by mammalian polo-like kinase 1. Proc. Natl Acad. Sci. USA 108, 11446–11451 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  73. 73

    Uehara, R. & Goshima, G. Functional central spindle assembly requires de novo microtubule generation in the interchromosomal region during anaphase. J. Cell Biol. 191, 259–267 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  74. 74

    Petry, S., Groen, A. C., Ishihara, K., Mitchison, T. J. & Vale, R. D. Branching microtubule nucleation in Xenopus egg extracts mediated by augmin and TPX2. Cell 152, 768–777 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  75. 75

    Kamasaki, T. et al. Augmin-dependent microtubule nucleation at microtubule walls in the spindle. J. Cell Biol. 202, 25–33 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  76. 76

    Sánchez-Huertas, C. & Lüders, J. The augmin connection in the geometry of microtubule networks. Curr. Biol. 25, R294–R299 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. 77

    Lecland, N. & Lüders, J. The dynamics of microtubule minus ends in the human mitotic spindle. Nat. Cell Biol. 16, 770–778 (2014).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  78. 78

    Ito, A. & Goshima, G. Microcephaly protein Asp focuses the minus ends of spindle microtubules at the pole and within the spindle. J. Cell Biol. 211, 999–1009 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  79. 79

    Buster, D. W., Zhang, D. & Sharp, D. J. Poleward tubulin flux in spindles: regulation and function in mitotic cells. Mol. Biol. Cell 18, 3094–3104 (2007).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  80. 80

    Hofmann, N. R. Augmin's role in microtubule generation in plants. Plant Cell 24, 1304–1304 (2012).

    CAS  Article  Google Scholar 

  81. 81

    Hayward, D. & Wakefield, J. G. Chromatin-mediated microtubule nucleation in Drosophila syncytial embryos. Commun. Integr. Biol. 7, e28512 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  82. 82

    Petry, S. Mechanisms of mitotic spindle assembly. Annu. Rev. Biochem. 85, 659–683 (2016).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  83. 83

    Cullen, C. F., Deák, P., Glover, D. M. & Ohkura, H. mini spindles. J. Cell Biol. 146, 1005–1018 (1999).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  84. 84

    Andersen, S. S. et al. Mitotic chromatin regulates phosphorylation of Stathmin/Op18. Nature 389, 640–643 (1997).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  85. 85

    Andersen, S. S. Spindle assembly and the art of regulating microtubule dynamics by MAPs and Stathmin/Op18. Trends Cell Biol. 10, 261–267 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  86. 86

    Howard, J. & Hyman, A. A. Microtubule polymerases and depolymerases. Curr. Opin. Cell Biol. 19, 31–35 (2007).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  87. 87

    Kinoshita, K. Reconstitution of physiological microtubule dynamics using purified components. Science 294, 1340–1343 (2001).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  88. 88

    Brouhard, G. J. et al. XMAP215 is a processive microtubule polymerase. Cell 132, 79–88 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  89. 89

    Tournebize, R. et al. Control of microtubule dynamics by the antagonistic activities of XMAP215 and XKCM1 in Xenopus egg extracts. Nat. Cell Biol. 2, 13–19 (2000). References 87–89 show that motor proteins can also possess microtubule polymerase and depolymerase activity through which they regulate microtubule length.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  90. 90

    Desai, A., Verma, S., Mitchison, T. J. & Walczak, C. E. Kin I kinesins are microtubule-destabilizing enzymes. Cell 96, 69–78 (1999).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  91. 91

    Kinoshita, K., Habermann, B. & Hyman, A. A. XMAP215: a key component of the dynamic microtubule cytoskeleton. Trends Cell Biol. 12, 267–273 (2002).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  92. 92

    Mayr, M. I. et al. The human kinesin Kif18A is a motile microtubule depolymerase essential for chromosome congression. Curr. Biol. 17, 488–498 (2007).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  93. 93

    Weaver, L. N. et al. Kif18A uses a microtubule binding site in the tail for plus-end localization and spindle length regulation. Curr. Biol. 21, 1500–1506 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  94. 94

    Drechsler, H. & McAinsh, A. D. Kinesin-12 motors cooperate to suppress microtubule catastrophes and drive the formation of parallel microtubule bundles. Proc. Natl Acad. Sci. USA 113, E1635–E1644 (2016).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  95. 95

    Sturgill, E. G. et al. Kinesin-12 Kif15 targets kinetochore fibers through an intrinsic two-step mechanism. Curr. Biol. 24, 2307–2313 (2014).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  96. 96

    Zhu, C. et al. Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using RNA interference. Mol. Biol. Cell 16, 3187–3199 (2005).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  97. 97

    Sturgill, E. G., Norris, S. R., Guo, Y. & Ohi, R. Kinesin-5 inhibitor resistance is driven by kinesin-12. J. Cell Biol. 213, 213–227 (2016).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  98. 98

    Raaijmakers, J. A., Tanenbaum, M. E. & Medema, R. H. Systematic dissection of dynein regulators in mitosis. J. Cell Biol. 201, 201–215 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  99. 99

    Brugués, J., Nuzzo, V., Mazur, E. & Needleman, D. J. Nucleation and transport organize microtubules in metaphase spindles. Cell 149, 554–564 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. 100

    Elting, M. W., Hueschen, C. L., Udy, D. B. & Dumont, S. Force on spindle microtubule minus ends moves chromosomes. J. Cell Biol. 206, 245–256 (2014).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  101. 101

    Tsai, M.-Y. et al. A mitotic lamin B matrix induced by RanGTP required for spindle assembly. Science 311, 1887–1893 (2006).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  102. 102

    Ma, L. et al. Requirement for Nudel and dynein for assembly of the lamin B spindle matrix. Nat. Cell Biol. 11, 247–256 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  103. 103

    Jiang, H. et al. Phase transition of spindle-associated protein regulate spindle apparatus assembly. Cell 163, 108–122 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  104. 104

    Schweizer, N., Weiss, M. & Maiato, H. The dynamic spindle matrix. Curr. Opin. Cell Biol. 28, 1–7 (2014).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  105. 105

    Shi, C., Channels, W. E., Zheng, Y. & Iglesias, P. A. A computational model for the formation of lamin-B mitotic spindle envelope and matrix. Interface Focus 4, 20130063 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  106. 106

    Schweizer, N., Pawar, N., Weiss, M. & Maiato, H. An organelle-exclusion envelope assists mitosis and underlies distinct molecular crowding in the spindle region. J. Cell Biol. 210, 695–704 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  107. 107

    Zheng, Y. A membranous spindle matrix orchestrates cell division. Nat. Rev. Mol. Cell Biol. 11, 529–535 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  108. 108

    Lancaster, O. M. et al. Mitotic rounding alters cell geometry to ensure efficient bipolar spindle formation. Dev. Cell 25, 270–283 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  109. 109

    Goshima, G., Wollman, R., Stuurman, N., Scholey, J. M. & Vale, R. D. Length control of the metaphase spindle. Curr. Biol. 15, 1979–1988 (2005).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  110. 110

    Hildebrandt, E. R. & Hoyt, M. A. Mitotic motors in Saccharomyces cerevisiae. Biochim. Biophys. Acta 1496, 99–116 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  111. 111

    Domnitz, S. B., Wagenbach, M., Decarreau, J. & Wordeman, L. MCAK activity at microtubule tips regulates spindle microtubule length to promote robust kinetochore attachment. J. Cell Biol. 197, 231–237 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  112. 112

    Cassimeris, L. TOGp, the human homolog of XMAP215/Dis1, is required for centrosome integrity, spindle pole organization, and bipolar spindle assembly. Mol. Biol. Cell 15, 1580–1590 (2004).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  113. 113

    Reber, S. B. et al. XMAP215 activity sets spindle length by controlling the total mass of spindle microtubules. Nat. Cell Biol. 15, 1116–1122 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  114. 114

    Varga, V., Leduc, C., Bormuth, V., Diez, S. & Howard, J. Kinesin-8 motors act cooperatively to mediate length-dependent microtubule depolymerization. Cell 138, 1174–1183 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  115. 115

    Cai, S., Weaver, L. N., Ems-McClung, S. C. & Walczak, C. E. Kinesin-14 family proteins HSET/XCTK2 control spindle length by cross-linking and sliding microtubules. Mol. Biol. Cell 20, 1348–1359 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  116. 116

    Braun, M., Drummond, D. R., Cross, R. A. & McAinsh, A. D. The kinesin-14 Klp2 organizes microtubules into parallel bundles by an ATP-dependent sorting mechanism. Nat. Cell Biol. 11, 724–730 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  117. 117

    Goshima, G., Kiyomitsu, T., Yoda, K. & Yanagida, M. Human centromere chromatin protein hMis12, essential for equal segregation, is independent of CENP-A loading pathway. J. Cell Biol. 160, 25–39 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  118. 118

    Wühr, M. et al. Evidence for an upper limit to mitotic spindle length. Curr. Biol. 18, 1256–1261 (2008). This paper demonstrates that spindle scaling with cell size only occurs in small cells, whereas an upper limit restricts spindle size in large cells.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. 119

    Farhadifar, R. et al. Scaling, selection, and evolutionary dynamics of the mitotic spindle. Curr. Biol. 25, 732–740 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  120. 120

    Greenan, G. et al. Centrosome size sets mitotic spindle length in Caenorhabditis elegans embryos. Curr. Biol. 20, 353–358 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  121. 121

    Hara, Y. & Kimura, A. Cell-size-dependent spindle elongation in the Caenorhabditis elegans early embryo. Curr. Biol. 19, 1549–1554 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  122. 122

    Courtois, A., Schuh, M., Ellenberg, J. & Hiiragi, T. The transition from meiotic to mitotic spindle assembly is gradual during early mammalian development. J. Cell Biol. 198, 357–370 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  123. 123

    Crowder, M. E. et al. A comparative analysis of spindle morphometrics across metazoans. Curr. Biol. 25, 1542–1550 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  124. 124

    Good, M. C., Vahey, M. D., Skandarajah, A., Fletcher, D. A. & Heald, R. Cytoplasmic volume modulates spindle size during embryogenesis. Science 342, 856–860 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  125. 125

    Hazel, J. et al. Changes in cytoplasmic volume are sufficient to drive spindle scaling. Science 342, 853–856 (2013). Using droplets to restrict cytoplasmic volume and shape, references 124 and 125 show that spindle length correlates with cytoplasmic volume rather than diameter.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  126. 126

    Dumont, S. & Mitchison, T. J. Compression regulates mitotic spindle length by a mechanochemical switch at the poles. Curr. Biol. 19, 1086–1095 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  127. 127

    Novakova, L. et al. A balance between nuclear and cytoplasmic volumes controls spindle length. PLoS ONE 11, e0149535 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. 128

    Goehring, N. W. & Hyman, A. A. Organelle growth control through limiting pools of cytoplasmic components. Curr. Biol. 22, R330–R339 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  129. 129

    Decker, M. et al. Limiting amounts of centrosome material set centrosome size in C. elegans embryos. Curr. Biol. 21, 1259–1267 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  130. 130

    Bird, A. W. & Hyman, A. A. Building a spindle of the correct length in human cells requires the interaction between TPX2 & Aurora A. J. Cell Biol. 182, 289–300 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  131. 131

    Wilbur, J. D. & Heald, R. Mitotic spindle scaling during Xenopus development by kif2a and importin α. eLife 2, 765–717 (2013).

    Article  CAS  Google Scholar 

  132. 132

    Young, S., Besson, S. & Welburn, J. P. I. Length-dependent anisotropic scaling of spindle shape. Biol. Open 3, 1217–1223 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  133. 133

    Nicklas, R. B. & Gordon, G. W. The total length of spindle microtubules depends on the number of chromosomes present. J. Cell Biol. 100, 1–7 (1985).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  134. 134

    Basto, R. et al. Flies without centrioles. Cell 125, 1375–1386 (2006).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  135. 135

    Magidson, V. et al. The spatial arrangement of chromosomes during prometaphase facilitates spindle assembly. Cell 146, 555–567 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  136. 136

    Moutinho-Pereira, S. et al. Genes involved in centrosome-independent mitotic spindle assembly in Drosophila S2 cells. Proc. Natl Acad. Sci. USA 110, 19808–19813 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  137. 137

    Baumbach, J., Levesque, M. P. & Raff, J. W. Centrosome loss or amplification does not dramatically perturb global gene expression in Drosophila. Biol. Open 1, 983–993 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  138. 138

    Nam, H.-J., Naylor, R. M. & van Deursen, J. M. Centrosome dynamics as a source of chromosomal instability. Trends Cell Biol. 25, 65–73 (2015).

    CAS  Article  Google Scholar 

  139. 139

    Silkworth, W. T., Nardi, I. K., Paul, R., Mogilner, A. & Cimini, D. Timing of centrosome separation is important for accurate chromosome segregation. Mol. Biol. Cell 23, 401–411 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  140. 140

    Sir, J.-H. et al. Loss of centrioles causes chromosomal instability in vertebrate somatic cells. J. Cell Biol. 203, 747–756 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  141. 141

    Bazzi, H. & Anderson, K. V. Acentriolar mitosis activates a p53-dependent apoptosis pathway in the mouse embryo. Proc. Natl Acad. Sci. USA 111, E1491–E1500 (2014). References 134, 140 and 141 demonstrate that centrosome removal by genetic manipulation in a range of systems does not preclude spindle assembly in somatic cells.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  142. 142

    Zierhut, C. and Funabiki, H. Nucleosome functions in spindle assembly and nuclear envelope formation. Bioessays 37, 1074–1085 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  143. 143

    Lavia, P. The GTPase RAN regulates multiple steps of the centrosome life cycle. Chromosome Res. 24, 53–65 (2016).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  144. 144

    Hasegawa, K., Ryu, S. J. & Kalab, P. Chromosomal gain promotes formation of a steep RanGTP gradient that drives mitosis in aneuploid cells. J. Cell Biol. 200, 151–161 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  145. 145

    Kirschner, M. & Mitchison, T. Beyond self-assembly: from microtubules to morphogenesis. Cell 45, 329–342 (1986). In this paper, the authors present their theory that the dynamic instability of microtubules drives the 'search-and-capture' of kinetochores during spindle assembly.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  146. 146

    Shao, L., Kner, P., Rego, E. H. & Gustafsson, M. G. L. Super-resolution 3D microscopy of live whole cells using structured illumination. Nat. Methods 8, 1044–1046 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  147. 147

    Tulu, U. S., Rusan, N. M. & Wadsworth, P. Peripheral, non-centrosome-associated microtubules contribute to spindle formation in centrosome-containing cells. Curr. Biol. 13, 1894–1899 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  148. 148

    Schuh, M. & Ellenberg, J. Self-organization of MTOCs replaces centrosome function during acentrosomal spindle assembly in live mouse oocytes. Cell 130, 484–498 (2007).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  149. 149

    Hornick, J. E. et al. Amphiastral mitotic spindle assembly in vertebrate cells lacking centrosomes. Curr. Biol. 21, 598–605 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  150. 150

    Baumbach, J., Novak, Z. A., Raff, J. W. & Wainman, A. Dissecting the function and assembly of acentriolar microtubule organizing centers in Drosophila cells in vivo. PLoS Genet. 11, e1005261 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. 151

    Kleylein-Sohn, J. et al. Acentrosomal spindle organization renders cancer cells dependent on the kinesin HSET. J. Cell Sci. 125, 5391–5402 (2013).

    Article  CAS  Google Scholar 

  152. 152

    Wei, J.-H., Zhang, Z. C., Wynn, R. M. & Seemann, J. Gm130 regulates golgi-derived spindle assembly by activating tpx2 and capturing microtubules. Cell 162, 287–299 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  153. 153

    Sauer, G. et al. Proteome analysis of the human mitotic spindle. Mol. Cell. Proteomics 4, 35–43 (2005).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  154. 154

    Hutchins, J. R. A. et al. Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science 328, 593–599 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  155. 155

    McKinley, K. L. et al. The CENP-L-N complex forms a critical node in an integrated meshwork of interactions at the centromere–kinetochore interface. Mol. Cell 60, 886–898 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  156. 156

    Cheeseman, I. M. The kinetochore. Cold Spring Harb. Perspect. Biol. 6, a015826 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. 157

    Lampert, F. & Westermann, S. A blueprint for kinetochores — new insights into the molecular mechanics of cell division. Nat. Rev. Mol. Cell Biol. 12, 407–412 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  158. 158

    Cheeseman, I. M., Chappie, J. S., Wilson-Kubalek, E. M. & Desai, A. The conserved KMN network constitutes the core microtubule-binding site of the kinetochore. Cell 127, 983–997 (2006).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  159. 159

    Rieder, C. L. Kinetochore fiber formation in animal somatic cells: dueling mechanisms come to a draw. Chromosoma 114, 310–318 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  160. 160

    Booth, D. G., Hood, F. E., Prior, I. A. & Royle, S. J. A. TACC3/ch-TOG/clathrin complex stabilises kinetochore fibres by inter-microtubule bridging. EMBO J. 30, 906–919 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  161. 161

    Khodjakov, A. & Pines, J. Centromere tension: a divisive issue. Nat. Cell Biol. 12, 919–923 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  162. 162

    Godek, K. M., Kabeche, L. & Compton, D. A. Regulation of kinetochore-microtubule attachments through homeostatic control during mitosis. Nat. Rev. Mol. Cell Biol. 16, 57–64 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  163. 163

    Trivedi, P. & Stukenberg, P. T. A. Centromere-signaling network underlies the coordination among mitotic events. Trends Biochem. Sci. 41, 160–174 (2016).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  164. 164

    Etemad, B., Kuijt, T. E. F. & Kops, G. J. P. L. Kinetochore-microtubule attachment is sufficient to satisfy the human spindle assembly checkpoint. Nat. Commun. 6, 8987 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  165. 165

    Foley, E. A. & Kapoor, T. M. Microtubule attachment and spindle assembly checkpoint signalling at the kinetochore. Nat. Rev. Mol. Cell Biol. 14, 25–37 (2012).

    Article  CAS  Google Scholar 

  166. 166

    Musacchio, A. The molecular biology of spindle assembly checkpoint signaling dynamics. Curr. Biol. 25, R1002–R1018 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  167. 167

    Hinchcliffe, E. H., Miller, F. J., Cham, M., Khodjakov, A. & Sluder, G. Requirement of a centrosomal activity for cell cycle progression through G1 into S phase. Science 291, 1547–1550 (2001).

    CAS  Article  Google Scholar 

  168. 168

    Wong, Y. L. et al. Cell biology. Reversible centriole depletion with an inhibitor of Polo-like kinase 4. Science 348, 1155–1160 (2015). This paper shows that p53-deficient cells can continue to proliferate without centrioles.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  169. 169

    Quintyne, N. J., Reing, J. E., Hoffelder, D. R., Gollin, S. M. & Saunders, W. S. Spindle multipolarity is prevented by centrosomal clustering. Science 307, 127–129 (2005).

    CAS  Article  Google Scholar 

  170. 170

    Kwon, M. et al. Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes Dev. 22, 2189–2203 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  171. 171

    Ganem, N. J., Godinho, S. A. & Pellman, D. A mechanism linking extra centrosomes to chromosomal instability. Nature 460, 278–282 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  172. 172

    Silkworth, W. T., Nardi, I. K., Scholl, L. M. & Cimini, D. Multipolar spindle pole coalescence is a major source of kinetochore mis-attachment and chromosome mis-segregation in cancer cells. PLoS ONE 4, e6564 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. 173

    Kalinina, I. et al. Pivoting of microtubules around the spindle pole accelerates kinetochore capture. Nat. Cell Biol. 15, 82–87 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. 174

    Rieder, C. L. & Alexander, S. P. Kinetochores are transported poleward along a single astral microtubule during chromosome attachment to the spindle in newt lung cells. J. Cell Biol. 110, 81–95 (1990). This paper demonstrated the attachment of a microtubule to a kinetochore in live cells for the first time.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  175. 175

    Tanaka, K. et al. Molecular mechanisms of kinetochore capture by spindle microtubules. Nature 434, 987–994 (2005).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  176. 176

    Magidson, V. et al. Adaptive changes in the kinetochore architecture facilitate proper spindle assembly. Nat. Cell Biol. 17, 1134–1144 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  177. 177

    Mishra, R. K., Chakraborty, P., Arnaoutov, A., Fontoura, B. M. A. & Dasso, M. The Nup107-160 complex and γ-TuRC regulate microtubule polymerization at kinetochores. Nat. Cell Biol. 12, 164–169 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  178. 178

    Stumpff, J., von Dassow, G., Wagenbach, M., Asbury, C. & Wordeman, L. The kinesin-8 motor Kif18A suppresses kinetochore movements to control mitotic chromosome alignment. Dev. Cell 14, 252–262 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  179. 179

    Gudimchuk, N. et al. Kinetochore kinesin CENP-E is a processive bi-directional tracker of dynamic microtubule tips. Nat. Cell Biol. 15, 1079–1088 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  180. 180

    Moores, C. A. Lucky 13 — microtubule depolymerisation by kinesin-13 motors. J. Cell Sci. 119, 3905–3913 (2006).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank S. Royle and A. McAinsh for critical reading of the manuscript. They apologize to authors whose work they could not cite owing to space constraints. The work in the L.P. laboratory is funded by the Canadian Institute for Health Research (MOP 123468, MOP 130507, MOP 142492), the Natural Sciences and Engineering Research Council of Canada (RGPIN 355644–13), the Krembil Foundation, the Canadian Cancer Society and Genome Canada. L.P. holds a Canada Research Chair in Centrosome Biogenesis and Function. S.L.P. holds a European Union Horizon 2020 Marie Skłodowska-Curie Global Fellowship (No. 702601).

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Historical perspective of spindle assembly (PDF 138 kb)

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Glossary

Microtubule minus end

Microtubules are composed of 13 protofilaments formed by head-to-tail arrays of α- and β-tubulin dimers, which means that microtubules are polar structures with two distinct ends. The minus end is the slow-growing end of microtubules.

Microtubule plus end

The fast-growing end of microtubules.

Guanine nucleotide exchange factor

(GEF). A protein that activates GTPases by stimulating the release of GDP to allow the binding of GTP.

Chromokinesins

Microtubule plus end-directed motor proteins that bind to chromosome arms and contribute to metaphase chromosome alignment.

Abnormal spindle-like microcephaly-associated protein

(ASPM). The human orthologue of Drosophila melanogaster Asp, it contributes to mitotic spindle assembly; defective forms are associated with autosomal recessive primary microcephaly (MCPH).

Spindle equator

The widest part of the mitotic spindle. It is the area in the centre of the spindle where microtubules from the opposite poles overlap and the chromosomes align.

Microtubule catastrophe

The transition from microtubule growth to shrinkage that results in rapid microtubule disassembly.

Nuclear lamina

A dense fibrillar network of intermediate filaments, lamins and associated proteins, which lines the inner surface of the nuclear membrane.

Cell rounding

The shape change that most animal cells undergo as they enter mitosis. It is seen as a shift from a spread, elongated shape into a compact, spherical morphology.

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Prosser, S., Pelletier, L. Mitotic spindle assembly in animal cells: a fine balancing act. Nat Rev Mol Cell Biol 18, 187–201 (2017). https://doi.org/10.1038/nrm.2016.162

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