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Mechanisms underlying spindle assembly and robustness

Nature Reviews Molecular Cell Biology volume 24, pages 523–542 (2023)Cite this article

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Abstract

The microtubule-based spindle orchestrates chromosome segregation during cell division. Following more than a century of study, many components and pathways contributing to spindle assembly have been described, but how the spindle robustly assembles remains incompletely understood. This process involves the self-organization of a large number of molecular parts — up to hundreds of thousands in vertebrate cells — whose local interactions give rise to a cellular-scale structure with emergent architecture, mechanics and function. In this Review, we discuss key concepts in our understanding of spindle assembly, focusing on recent advances and the new approaches that enabled them. We describe the pathways that generate the microtubule framework of the spindle by driving microtubule nucleation in a spatially controlled fashion and present recent insights regarding the organization of individual microtubules into structural modules. Finally, we discuss the emergent properties of the spindle that enable robust chromosome segregation.

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Fig. 1: Overview of spindle assembly, from molecular parts to cellular-scale properties.
Fig. 2: Microtubule nucleation during spindle assembly.
Fig. 3: Structural modules in the spindle.
Fig. 4: K-fibre formation mechanisms.
Fig. 5: Mechanisms underlying spindle robustness: redundancy, anchorage and dynamics.
Fig. 6: Spindle material properties.
Fig. 7: Spindle scaling mechanisms.

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References

  1. Flemming, W. Zellsubstanz, kern und zelltheilung (Vogel, 1882).

  2. Santaguida, S. & Amon, A. Short- and long-term effects of chromosome mis-segregation and aneuploidy. Nat. Rev. Mol. Cell Biol. 16, 473–485 (2015).

    Article  CAS  PubMed  Google Scholar 

  3. Potapova, T. & Gorbsky, G. J. The consequences of chromosome segregation errors in mitosis and meiosis. Biology https://doi.org/10.3390/biology6010012 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Thawani, A. & Petry, S. Molecular insight into how gamma-TuRC makes microtubules. J. Cell Sci. https://doi.org/10.1242/jcs.245464 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Voter, W. A. & Erickson, H. P. The kinetics of microtubule assembly. Evidence for a two-stage nucleation mechanism. J. Biol. Chem. 259, 10430–10438 (1984).

    Article  CAS  PubMed  Google Scholar 

  6. Zupa, E., Liu, P., Wurtz, M., Schiebel, E. & Pfeffer, S. The structure of the gamma-TuRC: a 25-years-old molecular puzzle. Curr. Opin. Struct. Biol. 66, 15–21 (2021).

    Article  CAS  PubMed  Google Scholar 

  7. Liu, P. et al. Insights into the assembly and activation of the microtubule nucleator gamma-TuRC. Nature 578, 467–471 (2020).

    Article  CAS  PubMed  Google Scholar 

  8. Wieczorek, M. et al. Asymmetric molecular architecture of the human gamma-tubulin ring complex. Cell 180, 165–175.e16 (2020).

    Article  CAS  PubMed  Google Scholar 

  9. Consolati, T. et al. Microtubule nucleation properties of single human gammaTuRCs explained by their Cryo-EM structure. Dev. Cell 53, 603–617.e8 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Thawani, A. et al. The transition state and regulation of gamma-TuRC-mediated microtubule nucleation revealed by single molecule microscopy. eLife https://doi.org/10.7554/eLife.54253 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Thawani, A., Kadzik, R. S. & Petry, S. XMAP215 is a microtubule nucleation factor that functions synergistically with the gamma-tubulin ring complex. Nat. Cell Biol. 20, 575–585 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Flor-Parra, I., Iglesias-Romero, A. B. & Chang, F. The XMAP215 ortholog Alp14 promotes microtubule nucleation in fission yeast. Curr. Biol. 28, 1681–1691.e4 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. King, B. R. et al. XMAP215 and gamma-tubulin additively promote microtubule nucleation in purified solutions. Mol. Biol. Cell 31, 2187–2194 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gunzelmann, J. et al. The microtubule polymerase Stu2 promotes oligomerization of the gamma-TuSC for cytoplasmic microtubule nucleation. eLife https://doi.org/10.7554/eLife.39932 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Tsuchiya, K. et al. Ran-GTP is non-essential to activate NuMA for mitotic spindle-pole focusing but dynamically polarizes HURP near chromosomes. Curr. Biol. 31, 115–127.e3 (2021).

    Article  CAS  PubMed  Google Scholar 

  16. Sampaio, P., Rebollo, E., Varmark, H., Sunkel, C. E. & Gonzalez, C. Organized microtubule arrays in gamma-tubulin-depleted Drosophila spermatocytes. Curr. Biol. 11, 1788–1793 (2001).

    Article  CAS  PubMed  Google Scholar 

  17. Brunet, S. et al. Characterization of the TPX2 domains involved in microtubule nucleation and spindle assembly in Xenopus egg extracts. Mol. Biol. Cell 15, 5318–5328 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Imasaki, T. et al. CAMSAP2 organizes a gamma-tubulin-independent microtubule nucleation centre through phase separation. eLife https://doi.org/10.7554/eLife.77365 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  19. McKinley, K. L. & Cheeseman, I. M. Large-scale analysis of CRISPR/Cas9 cell-cycle knockouts reveals the diversity of p53-dependent responses to cell-cycle defects. Dev. Cell 40, 405–420.e2 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gudimchuk, N. B. & McIntosh, J. R. Regulation of microtubule dynamics, mechanics and function through the growing tip. Nat. Rev. Mol. Cell Biol. 22, 777–795 (2021).

    Article  CAS  PubMed  Google Scholar 

  21. Choi, Y. K., Liu, P., Sze, S. K., Dai, C. & Qi, R. Z. CDK5RAP2 stimulates microtubule nucleation by the gamma-tubulin ring complex. J. Cell Biol. 191, 1089–1095 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Liu, P., Choi, Y. K. & Qi, R. Z. NME7 is a functional component of the gamma-tubulin ring complex. Mol. Biol. Cell 25, 2017–2025 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Cota, R. R. et al. MZT1 regulates microtubule nucleation by linking gammaTuRC assembly to adapter-mediated targeting and activation. J. Cell Sci. 130, 406–419 (2017).

    CAS  PubMed  Google Scholar 

  24. Kollman, J. M. et al. Ring closure activates yeast gammaTuRC for species-specific microtubule nucleation. Nat. Struct. Mol. Biol. 22, 132–137 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Woodruff, J. B. et al. The centrosome is a selective condensate that nucleates microtubules by concentrating tubulin. Cell 169, 1066–1077.e10 (2017).

    Article  CAS  PubMed  Google Scholar 

  26. Baumgart, J. et al. Soluble tubulin is significantly enriched at mitotic centrosomes. J. Cell Biol. 218, 3977–3985 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. King, M. R. & Petry, S. Phase separation of TPX2 enhances and spatially coordinates microtubule nucleation. Nat. Commun. 11, 270 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Haren, L., Stearns, T. & Luders, J. Plk1-dependent recruitment of gamma-tubulin complexes to mitotic centrosomes involves multiple PCM components. PLoS ONE 4, e5976 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Lee, K. & Rhee, K. PLK1 phosphorylation of pericentrin initiates centrosome maturation at the onset of mitosis. J. Cell Biol. 195, 1093–1101 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Haren, L. et al. NEDD1-dependent recruitment of the gamma-tubulin ring complex to the centrosome is necessary for centriole duplication and spindle assembly. J. Cell Biol. 172, 505–515 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Luders, J., Patel, U. K. & Stearns, T. GCP-WD is a gamma-tubulin targeting factor required for centrosomal and chromatin-mediated microtubule nucleation. Nat. Cell Biol. 8, 137–147 (2006).

    Article  PubMed  Google Scholar 

  32. Fong, K. W., Choi, Y. K., Rattner, J. B. & Qi, R. Z. CDK5RAP2 is a pericentriolar protein that functions in centrosomal attachment of the gamma-tubulin ring complex. Mol. Biol. Cell 19, 115–125 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Gomez-Ferreria, M. A. et al. Human Cep192 is required for mitotic centrosome and spindle assembly. Curr. Biol. 17, 1960–1966 (2007).

    Article  CAS  PubMed  Google Scholar 

  34. Joukov, V., Walter, J. C. & De Nicolo, A. The Cep192-organized aurora A-Plk1 cascade is essential for centrosome cycle and bipolar spindle assembly. Mol. Cell 55, 578–591 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhang, X. et al. Sequential phosphorylation of Nedd1 by Cdk1 and Plk1 is required for targeting of the gammaTuRC to the centrosome. J. Cell Sci. 122, 2240–2251 (2009).

    Article  CAS  PubMed  Google Scholar 

  36. Zimmerman, W. C., Sillibourne, J., Rosa, J. & Doxsey, S. J. Mitosis-specific anchoring of gamma tubulin complexes by pericentrin controls spindle organization and mitotic entry. Mol. Biol. Cell 15, 3642–3657 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Rale, M. J., Romer, B.,  Mahon, B. P., Travis, S. M. & Petry, S. The conserved centrosomin motif, γTuNA, forms a dimer that directly activates microtubule nucleation by the γ-tubulin ring complex (γTuRC). eLife  https://doi.org/10.7554/eLife.80053 (2022).

  38. Tungadi, E. A., Ito, A., Kiyomitsu, T. & Goshima, G. Human microcephaly ASPM protein is a spindle pole-focusing factor that functions redundantly with CDK5RAP2. J. Cell Sci. 130, 3676–3684 (2017).

    CAS  PubMed  Google Scholar 

  39. Heald, R. et al. Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts. Nature 382, 420–425 (1996).

    Article  CAS  PubMed  Google Scholar 

  40. Matthies, H. J., McDonald, H. B., Goldstein, L. S. & Theurkauf, W. E. Anastral meiotic spindle morphogenesis: role of the non-claret disjunctional kinesin-like protein. J. Cell Biol. 134, 455–464 (1996).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  42. Zhang, H. & Dawe, R. K. Mechanisms of plant spindle formation. Chromosome Res. 19, 335–344 (2011).

    Article  CAS  PubMed  Google Scholar 

  43. Khodjakov, A., Cole, R. W., Oakley, B. R. & Rieder, C. L. Centrosome-independent mitotic spindle formation in vertebrates. Curr. Biol. 10, 59–67 (2000).

    Article  CAS  PubMed  Google Scholar 

  44. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  46. Bischoff, F. R. & Ponstingl, H. Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1. Nature 354, 80–82 (1991).

    Article  CAS  PubMed  Google Scholar 

  47. Gorlich, D., Pante, N., Kutay, U., Aebi, U. & Bischoff, F. R. Identification of different roles for RanGDP and RanGTP in nuclear protein import. EMBO J. 15, 5584–5594 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Cavazza, T. & Vernos, I. The RanGTP Pathway: from nucleo-cytoplasmic transport to spindle assembly and beyond. Front. Cell Dev. Biol. 3, 82 (2015).

    PubMed  Google Scholar 

  49. 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).

    Article  CAS  PubMed  Google Scholar 

  50. Nachury, M. V. et al. Importin beta is a mitotic target of the small GTPase Ran in spindle assembly. Cell 104, 95–106 (2001).

    Article  CAS  PubMed  Google Scholar 

  51. Wiese, C. et al. Role of importin-beta in coupling Ran to downstream targets in microtubule assembly. Science 291, 653–656 (2001).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  53. Kalab, 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  Google Scholar 

  54. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  56. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Ho, C. M. et al. Augmin plays a critical role in organizing the spindle and phragmoplast microtubule arrays in Arabidopsis. Plant. Cell 23, 2606–2618 (2011).

    Article  CAS  PubMed  Google Scholar 

  58. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. David, A. F. et al. Augmin accumulation on long-lived microtubules drives amplification and kinetochore-directed growth. J. Cell Biol. 218, 2150–2168 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Tariq, A., Green, L., Jeynes, J. C. G., Soeller, C. & Wakefield, J. G. In vitro reconstitution of branching microtubule nucleation. eLife https://doi.org/10.7554/eLife.49769 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Zhang, Y., Hong, X., Hua, S. & Jiang, K. Reconstitution and mechanistic dissection of the human microtubule branching machinery. J. Cell Biol. https://doi.org/10.1083/jcb.202109053 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Alfaro-Aco, R., Thawani, A. & Petry, S. Biochemical reconstitution of branching microtubule nucleation. eLife https://doi.org/10.7554/eLife.49797 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Song, J. G. et al. Mechanism of how augmin directly targets the gamma-tubulin ring complex to microtubules. J. Cell Biol. 217, 2417–2428 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Zhu, H., Coppinger, J. A., Jang, C. Y., Yates, J. R. III & Fang, G. FAM29A promotes microtubule amplification via recruitment of the NEDD1-gamma-tubulin complex to the mitotic spindle. J. Cell Biol. 183, 835–848 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Petry, S., Pugieux, C., Nedelec, F. J. & Vale, R. D. Augmin promotes meiotic spindle formation and bipolarity in Xenopus egg extracts. Proc. Natl Acad. Sci. USA 108, 14473–14478 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Almeida, A. C. et al. Augmin-dependent microtubule self-organization drives kinetochore fiber maturation in mammals. Cell Rep. 39, 110610 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Verma, V. & Maresca, T. J. Direct observation of branching MT nucleation in living animal cells. J. Cell Biol. 218, 2829–2840 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Thawani, A., Stone, H. A., Shaevitz, J. W. & Petry, S. Spatiotemporal organization of branched microtubule networks. eLife https://doi.org/10.7554/eLife.43890 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Setru, S. U. et al. A hydrodynamic instability drives protein droplet formation on microtubules to nucleate branches. Nat. Phys. 17, 493–498 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Roostalu, J., Cade, N. I. & Surrey, T. Complementary activities of TPX2 and chTOG constitute an efficient importin-regulated microtubule nucleation module. Nat. Cell Biol. 17, 1422–1434 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Reid, T. A. et al. Suppression of microtubule assembly kinetics by the mitotic protein TPX2. J. Cell Sci. 129, 1319–1328 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Luo, J. et al. The microtubule-associated protein EML3 regulates mitotic spindle assembly by recruiting the Augmin complex to spindle microtubules. J. Biol. Chem. 294, 5643–5656 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  76. Khodjakov, A., Copenagle, L., Gordon, M. B., Compton, D. A. & Kapoor, T. M. Minus-end capture of preformed kinetochore fibers contributes to spindle morphogenesis. J. Cell Biol. 160, 671–683 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Sikirzhytski, V. et al. Microtubules assemble near most kinetochores during early prometaphase in human cells. J. Cell Biol. 217, 2647–2659 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Renda, F. et al. Non-centrosomal microtubules at kinetochores promote rapid chromosome biorientation during mitosis in human cells. Curr. Biol. 32, 1049–1063.e4 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Orjalo, A. V. et al. The Nup107-160 nucleoporin complex is required for correct bipolar spindle assembly. Mol. Biol. Cell 17, 3806–3818 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  83. Rasala, B. A., Orjalo, A. V., Shen, Z., Briggs, S. & Forbes, D. J. ELYS is a dual nucleoporin/kinetochore protein required for nuclear pore assembly and proper cell division. Proc. Natl Acad. Sci. USA 103, 17801–17806 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Euteneuer, U., Ris, H. & Borisy, G. G. Polarity of kinetochore microtubules in Chinese hamster ovary cells after recovery from a colcemid block. J. Cell Biol. 97, 202–208 (1983).

    Article  CAS  PubMed  Google Scholar 

  86. Shrestha, R. L. & Draviam, V. M. Lateral to end-on conversion of chromosome-microtubule attachment requires kinesins CENP-E and MCAK. Curr. Biol. 23, 1514–1526 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Popova, J. V. et al. Genetic control of kinetochore-driven microtubule growth in Drosophila mitosis. Cells https://doi.org/10.3390/cells11142127 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Gassmann, R. et al. Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle. J. Cell Biol. 166, 179–191 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  92. Ohi, R., Sapra, T., Howard, J. & Mitchison, T. J. Differentiation of cytoplasmic and meiotic spindle assembly MCAK functions by Aurora B-dependent phosphorylation. Mol. Biol. Cell 15, 2895–2906 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  95. Trivedi, P. et al. The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex. Nat. Cell Biol. 21, 1127–1137 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Musacchio, A. On the role of phase separation in the biogenesis of membraneless compartments. EMBO J. 41, e109952 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Rebollo, E., Llamazares, S., Reina, J. & Gonzalez, C. Contribution of noncentrosomal microtubules to spindle assembly in Drosophila spermatocytes. PLoS Biol. 2, E8 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  98. So, C. et al. A liquid-like spindle domain promotes acentrosomal spindle assembly in mammalian oocytes. Science https://doi.org/10.1126/science.aat9557 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  99. Halpin, D., Kalab, P., Wang, J., Weis, K. & Heald, R. Mitotic spindle assembly around RCC1-coated beads in Xenopus egg extracts. PLoS Biol. 9, e1001225 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Wolff, I. D., Tran, M. V., Mullen, T. J., Villeneuve, A. M. & Wignall, S. M. Assembly of Caenorhabditis elegans acentrosomal spindles occurs without evident microtubule-organizing centers and requires microtubule sorting by KLP-18/kinesin-12 and MESP-1. Mol. Biol. Cell 27, 3122–3131 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Dumont, J. et al. A centriole- and RanGTP-independent spindle assembly pathway in meiosis I of vertebrate oocytes. J. Cell Biol. 176, 295–305 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Ma, N. et al. Poleward transport of TPX2 in the mammalian mitotic spindle requires dynein, Eg5, and microtubule flux. Mol. Biol. Cell 21, 979–988 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Heald, R., Tournebize, R., Habermann, A., Karsenti, E. & Hyman, A. Spindle assembly in Xenopus egg extracts: respective roles of centrosomes and microtubule self-organization. J. Cell Biol. 138, 615–628 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  105. Prosser, S. L. & Pelletier, L. Mitotic spindle assembly in animal cells: a fine balancing act. Nat. Rev. Mol. Cell Biol. 18, 187–201 (2017).

    Article  CAS  PubMed  Google Scholar 

  106. Gaska, I., Armstrong, M. E., Alfieri, A. & Forth, S. The mitotic crosslinking protein PRC1 acts like a mechanical dashpot to resist microtubule sliding. Dev. Cell 54, 367–378.e5 (2020).

    Article  CAS  PubMed  Google Scholar 

  107. Verde, F., Berrez, J. M., Antony, C. & Karsenti, E. Taxol-induced microtubule asters in mitotic extracts of Xenopus eggs: requirement for phosphorylated factors and cytoplasmic dynein. J. Cell Biol. 112, 1177–1187 (1991).

    Article  CAS  PubMed  Google Scholar 

  108. Gaglio, T., Saredi, A. & Compton, D. A. NuMA is required for the organization of microtubules into aster-like mitotic arrays. J. Cell Biol. 131, 693–708 (1995).

    Article  CAS  PubMed  Google Scholar 

  109. Surrey, T., Nedelec, F., Leibler, S. & Karsenti, E. Physical properties determining self-organization of motors and microtubules. Science 292, 1167–1171 (2001).

    Article  CAS  PubMed  Google Scholar 

  110. Tan, R., Foster, P. J., Needleman, D. J. & McKenney, R. J. Cooperative accumulation of dynein-dynactin at microtubule minus-ends drives microtubule network reorganization. Dev. Cell 44, 233–247.e4 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Bieling, P., Telley, I. A. & Surrey, T. A minimal midzone protein module controls formation and length of antiparallel microtubule overlaps. Cell 142, 420–432 (2010).

    Article  CAS  PubMed  Google Scholar 

  112. Wijeratne, S. & Subramanian, R. Geometry of antiparallel microtubule bundles regulates relative sliding and stalling by PRC1 and Kif4A. eLife https://doi.org/10.7554/eLife.32595 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Hannabuss, J. et al. Self-organization of minimal anaphase spindle midzone bundles. Curr. Biol. 29, 2120–2130.e7 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. McDonald, K. L., O’Toole, E. T., Mastronarde, D. N. & McIntosh, J. R. Kinetochore microtubules in PTK cells. J. Cell Biol. 118, 369–383 (1992).

    Article  CAS  PubMed  Google Scholar 

  115. Long, A. F., Kuhn, J. & Dumont, S. The mammalian kinetochore-microtubule interface: robust mechanics and computation with many microtubules. Curr. Opin. Cell Biol. 60, 60–67 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Kiewisz, R. et al. Three-dimensional structure of kinetochore-fibers in human mitotic spindles. eLife https://doi.org/10.7554/eLife.75459 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  118. O’Toole, E., Morphew, M. & McIntosh, J. R. Electron tomography reveals aspects of spindle structure important for mechanical stability at metaphase. Mol. Biol. Cell 31, 184–195 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  119. Drpic, D. et al. Chromosome segregation is biased by kinetochore size. Curr. Biol. 28, 1344–1356.e5 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Varga, V. et al. Yeast kinesin-8 depolymerizes microtubules in a length-dependent manner. Nat. Cell Biol. 8, 957–962 (2006).

    Article  CAS  PubMed  Google Scholar 

  122. Du, Y., English, C. A. & Ohi, R. The kinesin-8 Kif18A dampens microtubule plus-end dynamics. Curr. Biol. 20, 374–380 (2010).

    Article  CAS  PubMed  Google Scholar 

  123. Stumpff, J. et al. A tethering mechanism controls the processivity and kinetochore-microtubule plus-end enrichment of the kinesin-8 Kif18A. Mol. Cell 43, 764–775 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Dudka, D., Castrogiovanni, C., Liaudet, N., Vassal, H. & Meraldi, P. Spindle-length-dependent HURP localization allows centrosomes to control kinetochore-fiber plus-end dynamics. Curr. Biol. 29, 3563–3578.e6 (2019).

    Article  CAS  PubMed  Google Scholar 

  125. Zhai, Y., Kronebusch, P. J. & Borisy, G. G. Kinetochore microtubule dynamics and the metaphase-anaphase transition. J. Cell Biol. 131, 721–734 (1995).

    Article  CAS  PubMed  Google Scholar 

  126. Nicklas, R. B. & Koch, C. A. Chromosome micromanipulation. 3. Spindle fiber tension and the reorientation of mal-oriented chromosomes. J. Cell Biol. 43, 40–50 (1969).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. DeLuca, J. G. et al. Kinetochore microtubule dynamics and attachment stability are regulated by Hec1. Cell 127, 969–982 (2006).

    Article  CAS  PubMed  Google Scholar 

  128. Bakhoum, S. F., Genovese, G. & Compton, D. A. Deviant kinetochore microtubule dynamics underlie chromosomal instability. Curr. Biol. 19, 1937–1942 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Koffa, M. D. et al. HURP is part of a Ran-dependent complex involved in spindle formation. Curr. Biol. 16, 743–754 (2006).

    Article  CAS  PubMed  Google Scholar 

  130. Sillje, H. H., Nagel, S., Korner, R. & Nigg, E. A. HURP is a Ran-importin beta-regulated protein that stabilizes kinetochore microtubules in the vicinity of chromosomes. Curr. Biol. 16, 731–742 (2006).

    Article  CAS  PubMed  Google Scholar 

  131. Begley, M. A. et al. K-fiber bundles in the mitotic spindle are mechanically reinforced by Kif15. Mol. Biol. Cell 32, br11 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Nixon, F. M. et al. The mesh is a network of microtubule connectors that stabilizes individual kinetochore fibers of the mitotic spindle. eLife https://doi.org/10.7554/eLife.07635 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  133. Nicklas, R. B., Kubai, D. F. & Hays, T. S. Spindle microtubules and their mechanical associations after micromanipulation in anaphase. J. Cell Biol. 95, 91–104 (1982).

    Article  CAS  PubMed  Google Scholar 

  134. Kirschner, M. & Mitchison, T. Beyond self-assembly: from microtubules to morphogenesis. Cell 45, 329–342 (1986).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. 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).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Wynne, D. J. & Funabiki, H. Kinetochore function is controlled by a phospho-dependent coexpansion of inner and outer components. J. Cell Biol. 210, 899–916 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Sacristan, C. et al. Dynamic kinetochore size regulation promotes microtubule capture and chromosome biorientation in mitosis. Nat. Cell Biol. 20, 800–810 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Mitchison, T., Evans, L., Schulze, E. & Kirschner, M. Sites of microtubule assembly and disassembly in the mitotic spindle. Cell 45, 515–527 (1986).

    Article  CAS  PubMed  Google Scholar 

  141. 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).

    Article  CAS  PubMed  Google Scholar 

  142. Hueschen, C. L., Kenny, S. J., Xu, K. & Dumont, S. NuMA recruits dynein activity to microtubule minus-ends at mitosis. eLife https://doi.org/10.7554/eLife.29328 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  143. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Sikirzhytski, V. et al. Direct kinetochore-spindle pole connections are not required for chromosome segregation. J. Cell Biol. 206, 231–243 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Mastronarde, D. N., McDonald, K. L., Ding, R. & McIntosh, J. R. Interpolar spindle microtubules in PTK cells. J. Cell Biol. 123, 1475–1489 (1993).

    Article  CAS  PubMed  Google Scholar 

  146. Kajtez, J. et al. Overlap microtubules link sister k-fibres and balance the forces on bi-oriented kinetochores. Nat. Commun. 7, 10298 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Polak, B., Risteski, P., Lesjak, S. & Tolic, I. M. PRC1-labeled microtubule bundles and kinetochore pairs show one-to-one association in metaphase. EMBO Rep. 18, 217–230 (2017).

    Article  CAS  PubMed  Google Scholar 

  148. Mollinari, C. et al. PRC1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone. J. Cell Biol. 157, 1175–1186 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Kapitein, L. C. et al. Microtubule-driven multimerization recruits ase1p onto overlapping microtubules. Curr. Biol. 18, 1713–1717 (2008).

    Article  CAS  PubMed  Google Scholar 

  150. Subramanian, R. et al. Insights into antiparallel microtubule crosslinking by PRC1, a conserved nonmotor microtubule binding protein. Cell 142, 433–443 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Jagric, M., Risteski, P., Martincic, J., Milas, A. & Tolic, I. M. Optogenetic control of PRC1 reveals its role in chromosome alignment on the spindle by overlap length-dependent forces. eLife https://doi.org/10.7554/eLife.61170 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  152. Brinkley, B. R. & Cartwright, J. Jr. Cold-labile and cold-stable microtubules in the mitotic spindle of mammalian cells. Ann. N. Y. Acad. Sci. 253, 428–439 (1975).

    Article  CAS  PubMed  Google Scholar 

  153. Ohi, R., Burbank, K., Liu, Q. & Mitchison, T. J. Nonredundant functions of Kinesin-13s during meiotic spindle assembly. Curr. Biol. 17, 953–959 (2007).

    Article  CAS  PubMed  Google Scholar 

  154. Burbank, K. S., Groen, A. C., Perlman, Z. E., Fisher, D. S. & Mitchison, T. J. A new method reveals microtubule minus ends throughout the meiotic spindle. J. Cell Biol. 175, 369–375 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Yang, G. et al. Architectural dynamics of the meiotic spindle revealed by single-fluorophore imaging. Nat. Cell Biol. 9, 1233–1242 (2007).

    Article  CAS  PubMed  Google Scholar 

  156. Saxton, W. M. et al. Tubulin dynamics in cultured mammalian cells. J. Cell Biol. 99, 2175–2186 (1984).

    Article  CAS  PubMed  Google Scholar 

  157. Wandke, C. et al. Human chromokinesins promote chromosome congression and spindle microtubule dynamics during mitosis. J. Cell Biol. 198, 847–863 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Antonio, C. et al. Xkid, a chromokinesin required for chromosome alignment on the metaphase plate. Cell 102, 425–435 (2000).

    Article  CAS  PubMed  Google Scholar 

  159. Funabiki, H. & Murray, A. W. The Xenopus chromokinesin Xkid is essential for metaphase chromosome alignment and must be degraded to allow anaphase chromosome movement. Cell 102, 411–424 (2000).

    Article  CAS  PubMed  Google Scholar 

  160. Brouhard, G. J. & Hunt, A. J. Microtubule movements on the arms of mitotic chromosomes: polar ejection forces quantified in vitro. Proc. Natl Acad. Sci. USA 102, 13903–13908 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Ke, K., Cheng, J. & Hunt, A. J. The distribution of polar ejection forces determines the amplitude of chromosome directional instability. Curr. Biol. 19, 807–815 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Rieder, C. L. & Salmon, E. D. Motile kinetochores and polar ejection forces dictate chromosome position on the vertebrate mitotic spindle. J. Cell Biol. 124, 223–233 (1994).

    Article  CAS  PubMed  Google Scholar 

  163. Stout, J. R. et al. Kif18B interacts with EB1 and controls astral microtubule length during mitosis. Mol. Biol. Cell 22, 3070–3080 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Tanenbaum, M. E. et al. A complex of Kif18b and MCAK promotes microtubule depolymerization and is negatively regulated by Aurora kinases. Curr. Biol. 21, 1356–1365 (2011).

    Article  CAS  PubMed  Google Scholar 

  165. Dema, A., van Haren, J. & Wittmann, T. Optogenetic EB1 inactivation shortens metaphase spindles by disrupting cortical force-producing interactions with astral microtubules. Curr. Biol. 32, 1197–1205.e4 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Barisic, M. et al. Mitosis. Microtubule detyrosination guides chromosomes during mitosis. Science 348, 799–803 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. di Pietro, F., Echard, A. & Morin, X. Regulation of mitotic spindle orientation: an integrated view. EMBO Rep. 17, 1106–1130 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  168. Lechler, T. & Mapelli, M. Spindle positioning and its impact on vertebrate tissue architecture and cell fate. Nat. Rev. Mol. Cell Biol. 22, 691–708 (2021).

    Article  CAS  PubMed  Google Scholar 

  169. Thery, M. et al. The extracellular matrix guides the orientation of the cell division axis. Nat. Cell Biol. 7, 947–953 (2005).

    Article  CAS  PubMed  Google Scholar 

  170. Fink, J. et al. External forces control mitotic spindle positioning. Nat. Cell Biol. 13, 771–778 (2011).

    Article  CAS  PubMed  Google Scholar 

  171. Guild, J., Ginzberg, M. B., Hueschen, C. L., Mitchison, T. J. & Dumont, S. Increased lateral microtubule contact at the cell cortex is sufficient to drive mammalian spindle elongation. Mol. Biol. Cell 28, 1975–1983 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Schaefer, M., Shevchenko, A., Shevchenko, A. & Knoblich, J. A. A protein complex containing Inscuteable and the Galpha-binding protein Pins orients asymmetric cell divisions in Drosophila. Curr. Biol. 10, 353–362 (2000).

    Article  CAS  PubMed  Google Scholar 

  173. Gotta, M., Dong, Y., Peterson, Y. K., Lanier, S. M. & Ahringer, J. Asymmetrically distributed C. elegans homologs of AGS3/PINS control spindle position in the early embryo. Curr. Biol. 13, 1029–1037 (2003).

    Article  CAS  PubMed  Google Scholar 

  174. Du, Q. & Macara, I. G. Mammalian Pins is a conformational switch that links NuMA to heterotrimeric G proteins. Cell 119, 503–516 (2004).

    Article  CAS  PubMed  Google Scholar 

  175. Fielmich, L. E. et al. Optogenetic dissection of mitotic spindle positioning in vivo. eLife https://doi.org/10.7554/eLife.38198 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  176. Okumura, M., Natsume, T., Kanemaki, M. T. & Kiyomitsu, T. Dynein-dynactin-NuMA clusters generate cortical spindle-pulling forces as a multi-arm ensemble. eLife https://doi.org/10.7554/eLife.36559 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Wong, Y. L. et al. Cell biology. Reversible centriole depletion with an inhibitor of Polo-like kinase 4. Science 348, 1155–1160 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Chinen, T. et al. NuMA assemblies organize microtubule asters to establish spindle bipolarity in acentrosomal human cells. EMBO J. 39, e102378 (2020).

    Article  CAS  PubMed  Google Scholar 

  181. Merdes, A., Heald, R., Samejima, K., Earnshaw, W. C. & Cleveland, D. W. Formation of spindle poles by dynein/dynactin-dependent transport of NuMA. J. Cell Biol. 149, 851–862 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Hueschen, C. L., Galstyan, V., Amouzgar, M., Phillips, R. & Dumont, S. Microtubule end-clustering maintains a steady-state spindle shape. Curr. Biol. 29, 700–708.e5 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Echeverri, C. J., Paschal, B. M., Vaughan, K. T. & Vallee, R. B. Molecular characterization of the 50-kD subunit of dynactin reveals function for the complex in chromosome alignment and spindle organization during mitosis. J. Cell Biol. 132, 617–633 (1996).

    Article  CAS  PubMed  Google Scholar 

  185. Renna, C. et al. Organizational principles of the NuMA-Dynein interaction interface and implications for mitotic spindle functions. Structure 28, 820–829.e6 (2020).

    Article  CAS  PubMed  Google Scholar 

  186. Harborth, J., Wang, J., Gueth-Hallonet, C., Weber, K. & Osborn, M. Self assembly of NuMA: multiarm oligomers as structural units of a nuclear lattice. EMBO J. 18, 1689–1700 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Sun, M. et al. NuMA regulates mitotic spindle assembly, structural dynamics and function via phase separation. Nat. Commun. 12, 7157 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Ma, H. et al. NuMA forms condensates through phase separation to drive spindle pole assembly. J. Mol. Cell Biol. https://doi.org/10.1093/jmcb/mjab081 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  189. Mountain, V. et al. The kinesin-related protein, HSET, opposes the activity of Eg5 and cross-links microtubules in the mammalian mitotic spindle. J. Cell Biol. 147, 351–366 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Sawin, K. E., LeGuellec, K., Philippe, M. & Mitchison, T. J. Mitotic spindle organization by a plus-end-directed microtubule motor. Nature 359, 540–543 (1992).

    Article  CAS  PubMed  Google Scholar 

  193. Blangy, A. et al. Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo. Cell 83, 1159–1169 (1995).

    Article  CAS  PubMed  Google Scholar 

  194. Kashina, A. S., Scholey, J. M., Leszyk, J. D. & Saxton, W. M. An essential bipolar mitotic motor. Nature 384, 225 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Kapitein, L. C. et al. The bipolar mitotic kinesin Eg5 moves on both microtubules that it crosslinks. Nature 435, 114–118 (2005).

    Article  CAS  PubMed  Google Scholar 

  196. Raaijmakers, J. A. et al. Nuclear envelope-associated dynein drives prophase centrosome separation and enables Eg5-independent bipolar spindle formation. EMBO J. 31, 4179–4190 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Toso, A. et al. Kinetochore-generated pushing forces separate centrosomes during bipolar spindle assembly. J. Cell Biol. 184, 365–372 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Sturgill, E. G. & Ohi, R. Kinesin-12 differentially affects spindle assembly depending on its microtubule substrate. Curr. Biol. 23, 1280–1290 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Tanenbaum, M. E. et al. Kif15 cooperates with eg5 to promote bipolar spindle assembly. Curr. Biol. 19, 1703–1711 (2009).

    Article  CAS  PubMed  Google Scholar 

  200. Vanneste, D., Takagi, M., Imamoto, N. & Vernos, I. The role of Hklp2 in the stabilization and maintenance of spindle bipolarity. Curr. Biol. 19, 1712–1717 (2009).

    Article  CAS  PubMed  Google Scholar 

  201. Drechsler, H., McHugh, T., Singleton, M. R., Carter, N. J. & McAinsh, A. D. The Kinesin-12 Kif15 is a processive track-switching tetramer. eLife 3, e01724 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  202. Reinemann, D. N. et al. Collective force regulation in anti-parallel microtubule gliding by dimeric Kif15 kinesin motors. Curr. Biol. 27, 2810–2820.e6 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Umbreit, N. T. et al. Mechanisms generating cancer genome complexity from a single cell division error. Science https://doi.org/10.1126/science.aba0712 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  204. van Heesbeen, R. G., Tanenbaum, M. E. & Medema, R. H. Balanced activity of three mitotic motors is required for bipolar spindle assembly and chromosome segregation. Cell Rep. 8, 948–956 (2014).

    Article  PubMed  Google Scholar 

  205. Neahring, L., Cho, N. H. & Dumont, S. Opposing motors provide mechanical and functional robustness in the human spindle. Dev. Cell 56, 3006–3018.e5 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Mitchison, T. J. et al. Roles of polymerization dynamics, opposed motors, and a tensile element in governing the length of Xenopus extract meiotic spindles. Mol. Biol. Cell 16, 3064–3076 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Tanenbaum, M. E., Macurek, L., Galjart, N. & Medema, R. H. Dynein, Lis1 and CLIP-170 counteract Eg5-dependent centrosome separation during bipolar spindle assembly. EMBO J. 27, 3235–3245 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Ferenz, N. P., Paul, R., Fagerstrom, C., Mogilner, A. & Wadsworth, P. Dynein antagonizes eg5 by crosslinking and sliding antiparallel microtubules. Curr. Biol. 19, 1833–1838 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  211. Elting, M. W., Prakash, M., Udy, D. B. & Dumont, S. Mapping load-bearing in the mammalian spindle reveals local kinetochore fiber anchorage that provides mechanical isolation and redundancy. Curr. Biol. 27, 2112–2122.e5 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Suresh, P., Long, A. F. & Dumont, S. Microneedle manipulation of the mammalian spindle reveals specialized, short-lived reinforcement near chromosomes. eLife https://doi.org/10.7554/eLife.53807 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  213. Franck, A. D. et al. Tension applied through the Dam1 complex promotes microtubule elongation providing a direct mechanism for length control in mitosis. Nat. Cell Biol. 9, 832–837 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Akiyoshi, B. et al. Tension directly stabilizes reconstituted kinetochore-microtubule attachments. Nature 468, 576–579 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Skibbens, R. V. & Salmon, E. D. Micromanipulation of chromosomes in mitotic vertebrate tissue cells: tension controls the state of kinetochore movement. Exp. Cell Res. 235, 314–324 (1997).

    Article  CAS  PubMed  Google Scholar 

  216. Nicklas, R. B. & Staehly, C. A. Chromosome micromanipulation. I. The mechanics of chromosome attachment to the spindle. Chromosoma 21, 1–16 (1967).

    Article  CAS  PubMed  Google Scholar 

  217. Long, A. F., Suresh, P. & Dumont, S. Individual kinetochore-fibers locally dissipate force to maintain robust mammalian spindle structure. J. Cell Biol. 219, https://doi.org/10.1083/jcb.201911090 (2020).

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  219. Mitchison, T. J. Polewards microtubule flux in the mitotic spindle: evidence from photoactivation of fluorescence. J. Cell Biol. 109, 637–652 (1989).

    Article  CAS  PubMed  Google Scholar 

  220. Arpag, G., Lawrence, E. J., Farmer, V. J., Hall, S. L. & Zanic, M. Collective effects of XMAP215, EB1, CLASP2, and MCAK lead to robust microtubule treadmilling. Proc. Natl Acad. Sci. USA 117, 12847–12855 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  221. Miyamoto, D. T., Perlman, Z. E., Burbank, K. S., Groen, A. C. & Mitchison, T. J. The kinesin Eg5 drives poleward microtubule flux in Xenopus laevis egg extract spindles. J. Cell Biol. 167, 813–818 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Brust-Mascher, I., Sommi, P., Cheerambathur, D. K. & Scholey, J. M. Kinesin-5-dependent poleward flux and spindle length control in Drosophila embryo mitosis. Mol. Biol. Cell 20, 1749–1762 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  223. Cameron, L. A. et al. Kinesin 5-independent poleward flux of kinetochore microtubules in PtK1 cells. J. Cell Biol. 173, 173–179 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. Steblyanko, Y. et al. Microtubule poleward flux in human cells is driven by the coordinated action of four kinesins. EMBO J. 39, e105432 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Ganem, N. J., Upton, K. & Compton, D. A. Efficient mitosis in human cells lacking poleward microtubule flux. Curr. Biol. 15, 1827–1832 (2005).

    Article  CAS  PubMed  Google Scholar 

  226. Rogers, G. C. et al. Two mitotic kinesins cooperate to drive sister chromatid separation during anaphase. Nature 427, 364–370 (2004).

    Article  CAS  PubMed  Google Scholar 

  227. Matos, I. et al. Synchronizing chromosome segregation by flux-dependent force equalization at kinetochores. J. Cell Biol. 186, 11–26 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  228. Maiato, H., Khodjakov, A. & Rieder, C. L. Drosophila CLASP is required for the incorporation of microtubule subunits into fluxing kinetochore fibres. Nat. Cell Biol. 7, 42–47 (2005).

    Article  CAS  PubMed  Google Scholar 

  229. Maffini, S. et al. Motor-independent targeting of CLASPs to kinetochores by CENP-E promotes microtubule turnover and poleward flux. Curr. Biol. 19, 1566–1572 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  230. Girao, H. et al. CLASP2 binding to curved microtubule tips promotes flux and stabilizes kinetochore attachments. J. Cell Biol. https://doi.org/10.1083/jcb.201905080 (2020).

    Article  PubMed  Google Scholar 

  231. Maddox, P., Straight, A., Coughlin, P., Mitchison, T. J. & Salmon, E. D. Direct observation of microtubule dynamics at kinetochores in Xenopus extract spindles: implications for spindle mechanics. J. Cell Biol. 162, 377–382 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. Nicklas, R. B. Measurements of the force produced by the mitotic spindle in anaphase. J. Cell Biol. 97, 542–548 (1983).

    Article  CAS  PubMed  Google Scholar 

  233. Garzon-Coral, C., Fantana, H. A. & Howard, J. A force-generating machinery maintains the spindle at the cell center during mitosis. Science 352, 1124–1127 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. Miller, M. P., Asbury, C. L. & Biggins, S. A TOG protein confers tension sensitivity to kinetochore-microtubule attachments. Cell 165, 1428–1439 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. Chen, G. Y. et al. Tension promotes kinetochore-microtubule release by Aurora B kinase. J. Cell Biol. https://doi.org/10.1083/jcb.202007030 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  236. Begg, D. A. & Ellis, G. W. Micromanipulation studies of chromosome movement. I. Chromosome-spindle attachment and the mechanical properties of chromosomal spindle fibers. J. Cell Biol. 82, 528–541 (1979).

    Article  CAS  PubMed  Google Scholar 

  237. Itabashi, T. et al. Probing the mechanical architecture of the vertebrate meiotic spindle. Nat. Methods 6, 167–172 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  238. Shimamoto, Y., Maeda, Y. T., Ishiwata, S., Libchaber, A. J. & Kapoor, T. M. Insights into the micromechanical properties of the metaphase spindle. Cell 145, 1062–1074 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  239. Takagi, J., Sakamoto, R., Shiratsuchi, G., Maeda, Y. T. & Shimamoto, Y. Mechanically distinct microtubule arrays determine the length and force response of the meiotic spindle. Dev. Cell 49, 267–278.e5 (2019).

    Article  CAS  PubMed  Google Scholar 

  240. Carlini, L., Brittingham, G. P., Holt, L. J. & Kapoor, T. M. Microtubules enhance mesoscale effective diffusivity in the crowded metaphase cytoplasm. Dev. Cell 54, 574–582.e4 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  241. Biswas, A., Kim, K., Cojoc, G., Guck, J. & Reber, S. The Xenopus spindle is as dense as the surrounding cytoplasm. Dev. Cell 56, 967–975.e5 (2021).

    Article  CAS  PubMed  Google Scholar 

  242. Brugues, J. & Needleman, D. Physical basis of spindle self-organization. Proc. Natl Acad. Sci. USA 111, 18496–18500 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  243. Oriola, D., Julicher, F. & Brugues, J. Active forces shape the metaphase spindle through a mechanical instability. Proc. Natl Acad. Sci. USA 117, 16154–16159 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  244. Roostalu, J., Rickman, J., Thomas, C., Nedelec, F. & Surrey, T. Determinants of polar versus nematic organization in networks of dynamic microtubules and mitotic motors. Cell 175, 796–808.e14 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  245. Novak, M. et al. The mitotic spindle is chiral due to torques within microtubule bundles. Nat. Commun. 9, 3571 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  246. Trupinic, M. et al. The chirality of the mitotic spindle provides a mechanical response to forces and depends on microtubule motors and augmin. Curr. Biol. https://doi.org/10.1016/j.cub.2022.04.035 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  247. Velle, K. B. et al. Naegleria’s mitotic spindles are built from unique tubulins and highlight core spindle features. Curr. Biol. 32, 1247–1261.e6 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  248. Yajima, J., Mizutani, K. & Nishizaka, T. A torque component present in mitotic kinesin Eg5 revealed by three-dimensional tracking. Nat. Struct. Mol. Biol. 15, 1119–1121 (2008).

    Article  CAS  PubMed  Google Scholar 

  249. Maruyama, Y. et al. CYK4 relaxes the bias in the off-axis motion by MKLP1 kinesin-6. Commun. Biol. 4, 180 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  250. Bormuth, V. et al. The highly processive kinesin-8, Kip3, switches microtubule protofilaments with a bias toward the left. Biophys. J. 103, L4–L6 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  251. Elshenawy, M. M. et al. Cargo adaptors regulate stepping and force generation of mammalian dynein-dynactin. Nat. Chem. Biol. 15, 1093–1101 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  252. Mitra, A. et al. Kinesin-14 motors drive a right-handed helical motion of antiparallel microtubules around each other. Nat. Commun. 11, 2565 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  253. Nitzsche, B. et al. Working stroke of the kinesin-14, ncd, comprises two substeps of different direction. Proc. Natl Acad. Sci. USA 113, E6582–E6589 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  254. Wuhr, M. et al. Evidence for an upper limit to mitotic spindle length. Curr. Biol. 18, 1256–1261 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  256. Milunovic-Jevtic, A., Jevtic, P., Levy, D. L. & Gatlin, J. C. In vivo mitotic spindle scaling can be modulated by changing the levels of a single protein: the microtubule polymerase XMAP215. Mol. Biol. Cell 29, 1311–1317 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  258. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  259. Hazel, J. et al. Changes in cytoplasmic volume are sufficient to drive spindle scaling. Science 342, 853–856 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  260. Wilbur, J. D. & Heald, R. Mitotic spindle scaling during Xenopus development by kif2a and importin alpha. eLife 2, e00290 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  261. Rieckhoff, E. M. et al. Spindle scaling is governed by cell boundary regulation of microtubule nucleation. Curr. Biol. 30, 4973–4983.e10 (2020).

    Article  CAS  PubMed  Google Scholar 

  262. Miller, K. E., Session, A. M. & Heald, R. Kif2a scales meiotic spindle size in Hymenochirus boettgeri. Curr. Biol. 29, 3720–3727.e5 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  263. Loughlin, R., Wilbur, J. D., McNally, F. J., Nedelec, F. J. & Heald, R. Katanin contributes to interspecies spindle length scaling in Xenopus. Cell 147, 1397–1407 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  265. Helmke, K. J. & Heald, R. TPX2 levels modulate meiotic spindle size and architecture in Xenopus egg extracts. J. Cell Biol. 206, 385–393 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  266. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  267. Decker, F., Oriola, D., Dalton, B. & Brugues, J. Autocatalytic microtubule nucleation determines the size and mass of Xenopus laevis egg extract spindles. eLife https://doi.org/10.7554/eLife.31149 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  268. 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).

    Article  CAS  PubMed  Google Scholar 

  269. Burbank, K. S., Mitchison, T. J. & Fisher, D. S. Slide-and-cluster models for spindle assembly. Curr. Biol. 17, 1373–1383 (2007).

    Article  CAS  PubMed  Google Scholar 

  270. Knouse, K. A., Lopez, K. E., Bachofner, M. & Amon, A. Chromosome segregation fidelity in epithelia requires tissue architecture. Cell 175, 200–211.e13 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  271. Ponjavic, I., Vukusic, K. & Tolic, I. M. Expansion microscopy of the mitotic spindle. Methods Cell Biol. 161, 247–274 (2021).

    Article  PubMed  Google Scholar 

  272. Chen, B. C. et al. Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution. Science 346, 1257998 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  273. Sen, O., Harrison, J. U., Burroughs, N. J. & McAinsh, A. D. Kinetochore life histories reveal an Aurora-B-dependent error correction mechanism in anaphase. Dev. Cell 56, 3405 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  274. Pamula, M. C. et al. High-resolution imaging reveals how the spindle midzone impacts chromosome movement. J. Cell Biol. 218, 2529–2544 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  275. Yamashita, N. et al. Three-dimensional tracking of plus-tips by lattice light-sheet microscopy permits the quantification of microtubule growth trajectories within the mitotic apparatus. J. Biomed. Opt. 20, 101206 (2015).

    Article  PubMed  Google Scholar 

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Author notes

  1. These authors contributed equally: Venecia A Valdez, Lila Neahring.

Authors and Affiliations

  1. Molecular Biology, Princeton University, Princeton, NJ, USA

    Venecia A. Valdez & Sabine Petry

  2. Department of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, CA, USA

    Lila Neahring & Sophie Dumont

  3. Developmental & Stem Cell Biology Graduate Program, UCSF, San Francisco, CA, USA

    Lila Neahring & Sophie Dumont

  4. Department of Biochemistry & Biophysics, UCSF, San Francisco, CA, USA

    Sophie Dumont

  5. Chan Zuckerberg Biohub, San Francisco, CA, USA

    Sophie Dumont

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V.A.V. and L.N. created the first draft of the text and figures. All authors contributed equally to discussion, revision and editing of the manuscript.

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Glossary

Barrelling-type instability

A compression-induced deformation that is symmetric about the axis of compression such as a compression that transforms a cylinder into a barrel shape.

Biomolecular condensates

Micro-scale compartments that lack surrounding membranes and are formed through weak multivalent interactions, concentrating proteins and nucleic acids.

Biorientation

The state of a chromosome when both sister kinetochores are attached to microtubules linked to opposite spindle poles.

Catastrophe

A parameter of microtubule dynamic instability that describes the stochastic switching of a microtubule into a rapidly shrinking, depolymerizing state.

Chromokinesins

Microtubule plus-end-directed motors that bind to chromosome arms via specific DNA-binding motifs.

CLASPs

TOG domain-containing proteins that recognize microtubule plus ends, where they suppress catastrophe and promote rescue.

Elasticity

Ability of a material, by storing energy, to return to its original shape after being deformed. The stiffness (elastic modulus) determines the magnitude of a deformation.

Emergent properties

Properties of an ensemble, produced by interactions between smaller components, that the smaller components in isolation do not exhibit.

Metaphase plate

The plane formed by chromosomes after alignment at metaphase, located at the spindle equator.

NDC80 complex

The core outer kinetochore protein complex that mediates direct binding to microtubules. The NDC80 complex consists of four subunits (Hec1/Ndc80, Nuf2, Spc24 and Spc25) and is present in multiple copies per kinetochore.

Nematic

The liquid crystal phase in which filaments of mixed polarity are roughly aligned in parallel.

Nucleoporin

(Nup). Broadly conserved family of proteins that comprise the nuclear pore complex, facilitating molecular transport between the cytoplasm and nucleus.

Pericentriolar material

(PCM). The dense, structured protein matrix, composed mainly of scaffold proteins and microtubule nucleation factors, that accumulates around centrioles to create the centrosome.

Polar ejection forces

Forces present during chromosome congression that push chromosome arms away from spindle poles.

Self-organization

A stable order arising from local interactions between energy-consuming parts.

Spindle assembly checkpoint

Signalling mechanism that monitors the attachment of kinetochores to spindle microtubules and inhibits progression of the cell cycle from metaphase to anaphase until sufficient attachments are made.

Stathmin

A protein that regulates microtubule dynamics by sequestering tubulin dimers, which destabilizes microtubules and inhibits their growth.

Rescue

A parameter of microtubule dynamic instability that describes the stochastic switching of a microtubule into a growing, polymerizing state.

Rheology

The study of the deformation and flow of materials with both solid and fluid characteristics.

Viscosity

Internal friction resisting deformation of a material, stemming from rearrangement of its components. The viscous drag coefficient determines the timescale of a deformation.

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Valdez, V.A., Neahring, L., Petry, S. et al. Mechanisms underlying spindle assembly and robustness. Nat Rev Mol Cell Biol 24, 523–542 (2023). https://doi.org/10.1038/s41580-023-00584-0

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