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Molecular control of animal cell cytokinesis

Nature Cell Biology volume 14, pages 440–447 (2012)Cite this article

Cytokinesis is the process by which mitotic cells physically split in two following chromosome segregation. Dividing animal cells first ingress a cytokinetic furrow and then separate the plasma membrane by abscission. The general cytological events and several conserved molecular factors involved in cytokinesis have been known for many years. However, recent progress in microscopy, chemical genetics, biochemical reconstitution and biophysical methodology has tremendously increased our understanding of the underlying molecular mechanisms. We discuss how recent insights have led to refined models of the distinct steps of animal cell cytokinesis, including anaphase spindle reorganization, division plane specification, actomyosin ring assembly and contraction, and abscission. We highlight how molecular signalling pathways coordinate the individual events to ensure faithful partitioning of the genome to emerging daughter cells.

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Figure 1: Overview of animal cell cytokinesis.
Figure 2: Central spindle assembly.
Figure 3: Division plane specification and the RhoA pathway.
Figure 4: The intercellular bridge and abscission.

References

  1. Pines, J. Mitosis: a matter of getting rid of the right protein at the right time. Trends Cell Biol. 16, 55–63 (2006).

    CAS  Google Scholar 

  2. Wurzenberger, C. & Gerlich, D. W. Phosphatases: providing safe passage through mitotic exit. Nat. Rev. Mol. Cell Biol. 12, 469–482 (2011).

    Article  CAS  PubMed  Google Scholar 

  3. Steigemann, P. et al. Aurora B-mediated abscission checkpoint protects against tetraploidization. Cell 136, 473–484 (2009).

    Article  PubMed  CAS  Google Scholar 

  4. Norden, C. et al. The NoCut pathway links completion of cytokinesis to spindle midzone function to prevent chromosome breakage. Cell 125, 85–98 (2006).

    Article  CAS  PubMed  Google Scholar 

  5. Mendoza, M. et al. A mechanism for chromosome segregation sensing by the NoCut checkpoint. Nat. Cell Biol. 11, 477–483 (2009).

    Article  CAS  PubMed  Google Scholar 

  6. Bi, E. et al. Involvement of an actomyosin contractile ring in Saccharomyces cerevisiae cytokinesis. J. Cell Biol. 142, 1301–1312 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Daga, R. R. & Chang, F. Dynamic positioning of the fission yeast cell division plane. Proc. Natl Acad. Sci. USA 102, 8228–8232 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jurgens, G. Plant cytokinesis: fission by fusion. Trends Cell Biol. 15, 277–283 (2005).

    Article  PubMed  CAS  Google Scholar 

  9. Barr, F. A. & Gruneberg, U. Cytokinesis: placing and making the final cut. Cell 131, 847–860 (2007).

    Article  CAS  PubMed  Google Scholar 

  10. Balasubramanian, M. K., Bi, E. & Glotzer, M. Comparative analysis of cytokinesis in budding yeast, fission yeast and animal cells. Curr. Biol. 14, R806–R818 (2004).

    Article  CAS  PubMed  Google Scholar 

  11. Otegui, M. S., Verbrugghe, K. J. & Skop, A. R. Midbodies and phragmoplasts: analogous structures involved in cytokinesis. Trends Cell Biol. 15, 404–413 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Glotzer, M. The 3Ms of central spindle assembly: microtubules, motors and MAPs. Nat. Rev. Mol. Cell Biol. 10, 9–20 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. 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 

  15. Jiang, W. et al. PRC1: a human mitotic spindle-associated CDK substrate protein required for cytokinesis. Mol. Cell 2, 877–885 (1998).

    Article  CAS  PubMed  Google Scholar 

  16. 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 

  17. 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 

  18. Zhu, C., Lau, E., Schwarzenbacher, R., Bossy-Wetzel, E. & Jiang, W. Spatiotemporal control of spindle midzone formation by PRC1 in human cells. Proc. Natl Acad. Sci. USA 103, 6196–6201 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mishima, M., Kaitna, S. & Glotzer, M. Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity. Dev. Cell 2, 41–54 (2002).

    Article  CAS  PubMed  Google Scholar 

  20. Pavicic-Kaltenbrunner, V., Mishima, M. & Glotzer, M. Cooperative assembly of CYK-4/MgcRacGAP and ZEN-4/MKLP1 to form the centralspindlin complex. Mol. Biol. Cell 18, 4992–5003 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hutterer, A., Glotzer, M. & Mishima, M. Clustering of centralspindlin is essential for its accumulation to the central spindle and the midbody. Curr. Biol. 19, 2043–2049 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Mishima, M., Pavicic, V., Gruneberg, U., Nigg, E. A. & Glotzer, M. Cell cycle regulation of central spindle assembly. Nature 430, 908–913 (2004).

    Article  CAS  PubMed  Google Scholar 

  23. Guse, A., Mishima, M. & Glotzer, M. Phosphorylation of ZEN-4/MKLP1 by aurora B regulates completion of cytokinesis. Curr. Biol. 15, 778–786 (2005).

    Article  CAS  PubMed  Google Scholar 

  24. Douglas, M. E., Davies, T., Joseph, N. & Mishima, M. Aurora B and 14-3-3 coordinately regulate clustering of centralspindlin during cytokinesis. Curr. Biol. 20, 927–933 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Neef, R., Klein, U. R., Kopajtich, R. & Barr, F. A. Cooperation between mitotic kinesins controls the late stages of cytokinesis. Curr. Biol. 16, 301–307 (2006).

    Article  CAS  PubMed  Google Scholar 

  26. Vazquez-Novelle, M. D. & Petronczki, M. Relocation of the chromosomal passenger complex prevents mitotic checkpoint engagement at anaphase. Curr. Biol. 20, 1402–1407 (2010).

    Article  CAS  PubMed  Google Scholar 

  27. Powers, J., Bossinger, O., Rose, D., Strome, S. & Saxton, W. A nematode kinesin required for cleavage furrow advancement. Curr. Biol. 8, 1133–1136 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hummer, S. & Mayer, T. U. Cdk1 negatively regulates midzone localization of the mitotic kinesin Mklp2 and the chromosomal passenger complex. Curr. Biol. 19, 607–612 (2009).

    Article  PubMed  CAS  Google Scholar 

  29. Sumara, I. et al. A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells. Dev. Cell 12, 887–900 (2007).

    Article  CAS  PubMed  Google Scholar 

  30. Ramadan, K. et al. Cdc48/p97 promotes reformation of the nucleus by extracting the kinase Aurora B from chromatin. Nature 450, 1258–1262 (2007).

    Article  CAS  PubMed  Google Scholar 

  31. Ban, R., Irino, Y., Fukami, K. & Tanaka, H. Human mitotic spindle-associated protein PRC1 inhibits MgcRacGAP activity toward Cdc42 during the metaphase. J. Biol. Chem. 279, 16394–16402 (2004).

    Article  CAS  PubMed  Google Scholar 

  32. Lewellyn, L., Carvalho, A., Desai, A., Maddox, A. S. & Oegema, K. The chromosomal passenger complex and centralspindlin independently contribute to contractile ring assembly. J. Cell Biol. 193, 155–169 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hu, C. K., Coughlin, M., Field, C. M. & Mitchison, T. J. KIF4 regulates midzone length during cytokinesis. Curr. Biol. 21, 815–824 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Canman, J. C. et al. Determining the position of the cell division plane. Nature 424, 1074–1078 (2003).

    Article  CAS  PubMed  Google Scholar 

  35. Hu, C. K., Coughlin, M., Field, C. M. & Mitchison, T. J. Cell polarization during monopolar cytokinesis. J. Cell Biol. 181, 195–202 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Neef, R. et al. Choice of Plk1 docking partners during mitosis and cytokinesis is controlled by the activation state of Cdk1. Nat. Cell Biol. 9, 436–444 (2007).

    Article  CAS  PubMed  Google Scholar 

  37. Neef, R. et al. Phosphorylation of mitotic kinesin-like protein 2 by polo-like kinase 1 is required for cytokinesis. J. Cell Biol. 162, 863–875 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Thery, M., Jimenez-Dalmaroni, A., Racine, V., Bornens, M. & Julicher, F. Experimental and theoretical study of mitotic spindle orientation. Nature 447, 493–496 (2007).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  40. Gibson, W. T. et al. Control of the mitotic cleavage plane by local epithelial topology. Cell 144, 427–438 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Minc, N., Burgess, D. & Chang, F. Influence of cell geometry on division-plane positioning. Cell 144, 414–426 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Von Dassow, G. Concurrent cues for cytokinetic furrow induction in animal cells. Trends Cell Biol. 19, 165–173 (2009).

    Article  CAS  PubMed  Google Scholar 

  43. Bringmann, H. & Hyman, A. A. A cytokinesis furrow is positioned by two consecutive signals. Nature 436, 731–734 (2005).

    Article  CAS  PubMed  Google Scholar 

  44. Dechant, R. & Glotzer, M. Centrosome separation and central spindle assembly act in redundant pathways that regulate microtubule density and trigger cleavage furrow formation. Dev. Cell 4, 333–344 (2003).

    Article  CAS  PubMed  Google Scholar 

  45. Werner, M., Munro, E. & Glotzer, M. Astral signals spatially bias cortical myosin recruitment to break symmetry and promote cytokinesis. Curr. Biol. 17, 1286–1297 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bement, W. M., Benink, H. A. & von Dassow, G. A microtubule-dependent zone of active RhoA during cleavage plane specification. J. Cell Biol. 170, 91–101 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Motegi, F., Velarde, N. V., Piano, F. & Sugimoto, A. Two phases of astral microtubule activity during cytokinesis in C. elegans embryos. Dev. Cell 10, 509–520 (2006).

    Article  CAS  PubMed  Google Scholar 

  48. Murthy, K. & Wadsworth, P. Dual role for microtubules in regulating cortical contractility during cytokinesis. J. Cell Sci. 121, 2350–2359 (2008).

    Article  CAS  PubMed  Google Scholar 

  49. Foe, V. E. & von Dassow, G. Stable and dynamic microtubules coordinately shape the myosin activation zone during cytokinetic furrow formation. J. Cell Biol. 183, 457–470 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Odell, G. M. & Foe, V. E. An agent-based model contrasts opposite effects of dynamic and stable microtubules on cleavage furrow positioning. J. Cell Biol. 183, 471–483 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Yuce, O., Piekny, A. & Glotzer, M. An ECT2-centralspindlin complex regulates the localization and function of RhoA. J. Cell Biol. 170, 571–582 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Nishimura, Y. & Yonemura, S. Centralspindlin regulates ECT2 and RhoA accumulation at the equatorial cortex during cytokinesis. J. Cell Sci. 119, 104–114 (2006).

    Article  CAS  PubMed  Google Scholar 

  53. Zhao, W. M. & Fang, G. Anillin is a substrate of anaphase-promoting complex/cyclosome (APC/C) that controls spatial contractility of myosin during late cytokinesis. J. Biol. Chem. 280, 33516–33524 (2005).

    Article  CAS  PubMed  Google Scholar 

  54. Petronczki, M., Glotzer, M., Kraut, N. & Peters, J. M. Polo-like kinase 1 triggers the initiation of cytokinesis in human cells by promoting recruitment of the RhoGEF Ect2 to the central spindle. Dev. Cell 12, 713–725 (2007).

    Article  CAS  PubMed  Google Scholar 

  55. Wolfe, B. A., Takaki, T., Petronczki, M. & Glotzer, M. Polo-like kinase 1 directs assembly of the HsCyk-4 RhoGAP/Ect2 RhoGEF complex to initiate cleavage furrow formation. PLoS Biol. 7, e1000110 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Su, K. C., Takaki, T. & Petronczki, M. Targeting of the RhoGEF Ect2 to the equatorial membrane controls cleavage furrow formation during cytokinesis. Dev. Cell 21, 1104–1115 (2011).

    Article  CAS  PubMed  Google Scholar 

  57. Birkenfeld, J. et al. GEF-H1 modulates localized RhoA activation during cytokinesis under the control of mitotic kinases. Dev. Cell 12, 699–712 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Miller, A. L. & Bement, W. M. Regulation of cytokinesis by Rho GTPase flux. Nat. Cell Biol. 11, 71–77 (2009).

    Article  CAS  PubMed  Google Scholar 

  59. Loria, A., Longhini, K. M. & Glotzer, M. The RhoGAP domain of CYK-4 has an essential role in RhoA activation. Curr. Biol. 22, 213–219 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Canman, J. C. et al. Inhibition of Rac by the GAP activity of centralspindlin is essential for cytokinesis. Science 322, 1543–1546 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Vale, R. D., Spudich, J. A. & Griffis, E. R. Dynamics of myosin, microtubules, and Kinesin-6 at the cortex during cytokinesis in Drosophila S2 cells. J. Cell Biol. 186, 727–738 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Fuller, B. G. et al. Midzone activation of aurora B in anaphase produces an intracellular phosphorylation gradient. Nature 453, 1132–1136 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Von Dassow, G., Verbrugghe, K. J., Miller, A. L., Sider, J. R. & Bement, W. M. Action at a distance during cytokinesis. J. Cell Biol. 187, 831–845 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Severson, A. F., Baillie, D. L. & Bowerman, B. A Formin Homology protein and a profilin are required for cytokinesis and Arp2/3-independent assembly of cortical microfilaments in C. elegans. Curr. Biol. 12, 2066–2075 (2002).

    Article  CAS  PubMed  Google Scholar 

  65. Watanabe, S. et al. mDia2 induces the actin scaffold for the contractile ring and stabilizes its position during cytokinesis in NIH 3T3 cells. Mol. Biol. Cell 19, 2328–2338 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Castrillon, D. H. & Wasserman, S. A. Diaphanous is required for cytokinesis in Drosophila and shares domains of similarity with the products of the limb deformity gene. Development 120, 3367–3377 (1994).

    Article  CAS  PubMed  Google Scholar 

  67. Matsumura, F. Regulation of myosin II during cytokinesis in higher eukaryotes. Trends Cell Biol. 15, 371–377 (2005).

    Article  CAS  PubMed  Google Scholar 

  68. Zhou, M. & Wang, Y. L. Distinct pathways for the early recruitment of myosin II and actin to the cytokinetic furrow. Mol. Biol. Cell 19, 318–326 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Yumura, S., Ueda, M., Sako, Y., Kitanishi-Yumura, T. & Yanagida, T. Multiple mechanisms for accumulation of myosin II filaments at the equator during cytokinesis. Traffic 9, 2089–2099 (2008).

    Article  CAS  PubMed  Google Scholar 

  70. Uehara, R. et al. Determinants of myosin II cortical localization during cytokinesis. Curr. Biol. 20, 1080–1085 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Murthy, K. & Wadsworth, P. Myosin-II-dependent localization and dynamics of F-actin during cytokinesis. Curr. Biol. 15, 724–731 (2005).

    Article  CAS  PubMed  Google Scholar 

  72. Albertson, R., Cao, J., Hsieh, T. S. & Sullivan, W. Vesicles and actin are targeted to the cleavage furrow via furrow microtubules and the central spindle. J. Cell Biol. 181, 777–790 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Piekny, A. J. & Maddox, A. S. The myriad roles of Anillin during cytokinesis. Semin. Cell. Dev. Biol. 21, 881–891 (2010).

    Article  CAS  PubMed  Google Scholar 

  74. Piekny, A. J. & Glotzer, M. Anillin is a scaffold protein that links RhoA, actin, and myosin during cytokinesis. Curr. Biol. 18, 30–36 (2008).

    Article  CAS  PubMed  Google Scholar 

  75. Gregory, S. L. et al. Cell division requires a direct link between microtubule-bound RacGAP and Anillin in the contractile ring. Curr. Biol. 18, 25–29 (2008).

    Article  CAS  PubMed  Google Scholar 

  76. D'Avino, P. P. et al. Interaction between Anillin and RacGAP50C connects the actomyosin contractile ring with spindle microtubules at the cell division site. J. Cell Sci. 121, 1151–1158 (2008).

    Article  CAS  PubMed  Google Scholar 

  77. Echard, A., Hickson, G. R., Foley, E. & O'Farrell, P. H. Terminal cytokinesis events uncovered after an RNAi screen. Curr. Biol. 14, 1685–1693 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Reichl, E. M. et al. Interactions between myosin and actin crosslinkers control cytokinesis contractility dynamics and mechanics. Curr. Biol. 18, 471–480 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Maddox, A. S., Lewellyn, L., Desai, A. & Oegema, K. Anillin and the septins promote asymmetric ingression of the cytokinetic furrow. Dev. Cell 12, 827–835 (2007).

    Article  CAS  PubMed  Google Scholar 

  80. Estey, M. P., Di Ciano-Oliveira, C., Froese, C. D., Bejide, M. T. & Trimble, W. S. Distinct roles of septins in cytokinesis: SEPT9 mediates midbody abscission. J. Cell Biol. 191, 741–749 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Dobbelaere, J. & Barral, Y. Spatial coordination of cytokinetic events by compartmentalization of the cell cortex. Science 305, 393–396 (2004).

    Article  CAS  PubMed  Google Scholar 

  82. Joo, E., Surka, M. C. & Trimble, W. S. Mammalian SEPT2 is required for scaffolding nonmuscle myosin II and its kinases. Dev. Cell 13, 677–690 (2007).

    Article  CAS  PubMed  Google Scholar 

  83. Brill, J. A., Wong, R. & Wilde, A. Phosphoinositide function in cytokinesis. Curr. Biol. 21, R930–R934 (2011).

    Article  CAS  PubMed  Google Scholar 

  84. Schroeder, T. E. The contractile ring II. Determining its brief existence, volumetric changes, and vital role in cleaving Arbacia eggs. J. Cell Biol. 53, 419–434 (1972).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Egelhoff, T. T., Lee, R. J. & Spudich, J. A. Dictyostelium myosin heavy chain phosphorylation sites regulate myosin filament assembly and localization in vivo. Cell 75, 363–371 (1993).

    Article  CAS  PubMed  Google Scholar 

  86. Tucker, J. B. Microtubules and a contractile ring of microfilaments associated with a cleavage furrow. J. Cell Sci. 8, 557–571 (1971).

    Article  CAS  PubMed  Google Scholar 

  87. Maupin, P. & Pollard, T. D. Arrangement of actin filaments and myosin-like filaments in the contractile ring and of actin-like filaments in the mitotic spindle of dividing HeLa cells. J. Ultrastruct. Mol. Struct. Res. 94, 92–103 (1986).

    Article  CAS  PubMed  Google Scholar 

  88. Kamasaki, T., Osumi, M. & Mabuchi, I. Three-dimensional arrangement of F-actin in the contractile ring of fission yeast. J. Cell Biol. 178, 765–771 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Fishkind, D. J. & Wang, Y. L. Orientation and three-dimensional organization of actin filaments in dividing cultured cells. J. Cell Biol. 123, 837–848 (1993).

    Article  CAS  PubMed  Google Scholar 

  90. Pollard, T. D. The role of actin in the temperature-dependent gelation and contraction of extracts of Acanthamoeba. J. Cell Biol. 68, 579–601 (1976).

    Article  CAS  PubMed  Google Scholar 

  91. Kruse, K. & Julicher, F. Self-organization and mechanical properties of active filament bundles. Phys. Rev. E Stat. Nonlin. Soft. Matter Phys. 67, 051913 (2003).

    Article  PubMed  CAS  Google Scholar 

  92. Carvalho, A., Desai, A. & Oegema, K. Structural memory in the contractile ring makes the duration of cytokinesis independent of cell size. Cell 137, 926–937 (2009).

    Article  CAS  PubMed  Google Scholar 

  93. Biron, D., Alvarez-Lacalle, E., Tlusty, T. & Moses, E. Molecular model of the contractile ring. Phys. Rev. Lett. 95, 098102 (2005).

    Article  CAS  PubMed  Google Scholar 

  94. Zumdieck, A., Kruse, K., Bringmann, H., Hyman, A. A. & Julicher, F. Stress generation and filament turnover during actin ring constriction. PLoS One 2, e696 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Calvert, M. E. et al. Myosin concentration underlies cell size-dependent scalability of actomyosin ring constriction. J. Cell Biol. 195, 799–813 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Rankin, K. E. & Wordeman, L. Long astral microtubules uncouple mitotic spindles from the cytokinetic furrow. J. Cell Biol. 190, 35–43 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Sedzinski, J. et al. Polar actomyosin contractility destabilizes the position of the cytokinetic furrow. Nature 476, 462–466 (2011).

    Article  CAS  PubMed  Google Scholar 

  98. Bluemink, J. G. & de Laat, S. W. New membrane formation during cytokinesis in normal and cytochalasin B-treated eggs of Xenopus laevis, I. Electron microscope observations. J. Cell Biol. 59, 89–108 (1973).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Shuster, C. B. & Burgess, D. R. Targeted new membrane addition in the cleavage furrow is a late, separate event in cytokinesis. Proc. Natl Acad. Sci. USA 99, 3633–3638 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Danilchik, M. V., Bedrick, S. D., Brown, E. E. & Ray, K. Furrow microtubules and localized exocytosis in cleaving Xenopus laevis embryos. J. Cell Sci. 116, 273–283 (2003).

    Article  CAS  PubMed  Google Scholar 

  101. Dyer, N. et al. Spermatocyte cytokinesis requires rapid membrane addition mediated by ARF6 on central spindle recycling endosomes. Development 134, 4437–4447 (2007).

    Article  CAS  PubMed  Google Scholar 

  102. Skop, A. R., Bergmann, D., Mohler, W. A. & White, J. G. Completion of cytokinesis in C. elegans requires a brefeldin A-sensitive membrane accumulation at the cleavage furrow apex. Curr. Biol. 11, 735–746 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Emoto, K., Inadome, H., Kanaho, Y., Narumiya, S. & Umeda, M. Local change in phospholipid composition at the cleavage furrow is essential for completion of cytokinesis. J. Biol. Chem. 280, 37901–37907 (2005).

    Article  CAS  PubMed  Google Scholar 

  104. Ng, M. M., Chang, F. & Burgess, D. R. Movement of membrane domains and requirement of membrane signaling molecules for cytokinesis. Dev. Cell 9, 781–790 (2005).

    Article  CAS  PubMed  Google Scholar 

  105. Guizetti, J. & Gerlich, D. W. Cytokinetic abscission in animal cells. Semin. Cell. Dev. Biol. 21, 909–916 (2010).

    Article  CAS  PubMed  Google Scholar 

  106. Steigemann, P. & Gerlich, D. W. Cytokinetic abscission: cellular dynamics at the midbody. Trends Cell Biol. 19, 606–616 (2009).

    Article  CAS  PubMed  Google Scholar 

  107. Skop, A. R., Liu, H., Yates, J. III, Meyer, B. J. & Heald, R. Dissection of the mammalian midbody proteome reveals conserved cytokinesis mechanisms. Science 305, 61–66 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Gromley, A. et al. Centriolin anchoring of exocyst and SNARE complexes at the midbody is required for secretory-vesicle-mediated abscission. Cell 123, 75–87 (2005).

    Article  CAS  PubMed  Google Scholar 

  109. Goss, J. W. & Toomre, D. K. Both daughter cells traffic and exocytose membrane at the cleavage furrow during mammalian cytokinesis. J. Cell Biol. 181, 1047–1054 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Schiel, J. A. et al. Endocytic membrane fusion and buckling-induced microtubule severing mediate cell abscission. J. Cell Sci. 124, 1411–1424 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Kouranti, I., Sachse, M., Arouche, N., Goud, B. & Echard, A. Rab35 regulates an endocytic recycling pathway essential for the terminal steps of cytokinesis. Curr. Biol. 16, 1719–1725 (2006).

    Article  CAS  PubMed  Google Scholar 

  112. Fielding, A. B. et al. Rab11-FIP3 and FIP4 interact with Arf6 and the exocyst to control membrane traffic in cytokinesis. EMBO J. 24, 3389–3399 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Low, S. H. et al. Syntaxin 2 and endobrevin are required for the terminal step of cytokinesis in mammalian cells. Dev. Cell 4, 753–759 (2003).

    Article  CAS  PubMed  Google Scholar 

  114. Pohl, C. & Jentsch, S. Final stages of cytokinesis and midbody ring formation are controlled by BRUCE. Cell 132, 832–845 (2008).

    Article  CAS  PubMed  Google Scholar 

  115. Baluska, F., Menzel, D. & Barlow, P. W. Cytokinesis in plant and animal cells: endosomes 'shut the door'. Dev. Biol. 294, 1–10 (2006).

    Article  CAS  PubMed  Google Scholar 

  116. Guizetti, J. et al. Cortical constriction during abscission involves helices of ESCRT-III-dependent filaments. Science 331, 1616–1620 (2011).

    Article  CAS  PubMed  Google Scholar 

  117. Carlton, J. G. & Martin-Serrano, J. Parallels between cytokinesis and retroviral budding: a role for the ESCRT machinery. Science 316, 1908–1912 (2007).

    Article  CAS  PubMed  Google Scholar 

  118. Carlton, J. G., Agromayor, M. & Martin-Serrano, J. Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release. Proc. Natl. Acad. Sci. USA 105, 10541–10546 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Morita, E. et al. Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis. EMBO J. 26, 4215–4227 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Hurley, J. H. & Hanson, P. I. Membrane budding and scission by the ESCRT machinery: it's all in the neck. Nat. Rev. Mol. Cell Biol. 11, 556–566 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Guizetti, J. & Gerlich, D. W. ESCRT-III polymers in membrane neck constriction. Trends Cell Biol. 22, 133–140 (2012).

    Article  CAS  PubMed  Google Scholar 

  122. Elia, N., Sougrat, R., Spurlin, T. A., Hurley, J. H. & Lippincott-Schwartz, J. Dynamics of endosomal sorting complex required for transport (ESCRT) machinery during cytokinesis and its role in abscission. Proc. Natl Acad. Sci. USA 108, 4846–4851 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Bastos, R. N. & Barr, F. A. Plk1 negatively regulates Cep55 recruitment to the midbody to ensure orderly abscission. J. Cell Biol. 191, 751–760 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Sagona, A. P. et al. PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody. Nat. Cell Biol. 12, 362–371 (2010).

    Article  CAS  PubMed  Google Scholar 

  125. Saurin, A. T. et al. The regulated assembly of a PKCɛ complex controls the completion of cytokinesis. Nat. Cell Biol. 10, 891–901 (2008).

    Article  CAS  PubMed  Google Scholar 

  126. Dambournet, D. et al. Rab35 GTPase and OCRL phosphatase remodel lipids and F-actin for successful cytokinesis. Nat. Cell Biol. 13, 981–988 (2011).

    Article  CAS  PubMed  Google Scholar 

  127. Connell, J. W., Lindon, C., Luzio, J. P. & Reid, E. Spastin couples microtubule severing to membrane traffic in completion of cytokinesis and secretion. Traffic 10, 42–56 (2009).

    Article  CAS  PubMed  Google Scholar 

  128. Yang, D. et al. Structural basis for midbody targeting of spastin by the ESCRT-III protein CHMP1B. Nat. Struct. Mol. Biol. 15, 1278–1286 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Lacroix, B. et al. Tubulin polyglutamylation stimulates spastin-mediated microtubule severing. J. Cell Biol. 189, 945–954 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Mackay, D. R., Makise, M. & Ullman, K. S. Defects in nuclear pore assembly lead to activation of an Aurora B-mediated abscission checkpoint. J. Cell Biol. 191, 923–931 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. 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 

  132. Ganem, N. J., Storchova, Z. & Pellman, D. Tetraploidy, aneuploidy and cancer. Curr. Opin. Genet. Dev. 17, 157–162 (2007).

    Article  CAS  PubMed  Google Scholar 

  133. Fujiwara, T. et al. Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature 437, 1043–1047 (2005).

    Article  CAS  PubMed  Google Scholar 

  134. Ettinger, A. W. et al. Proliferating versus differentiating stem and cancer cells exhibit distinct midbody-release behaviour. Nat. Commun. 2, 503 (2011).

    Article  PubMed  CAS  Google Scholar 

  135. Kuo, T. C. et al. Midbody accumulation through evasion of autophagy contributes to cellular reprogramming and tumorigenicity. Nat. Cell Biol. 13, 1214–1223 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Pohl, C. & Jentsch, S. Midbody ring disposal by autophagy is a post-abscission event of cytokinesis. Nat. Cell Biol. 11, 65–70 (2009).

    Article  CAS  PubMed  Google Scholar 

  137. Toomre, D. & Bewersdorf, J. A new wave of cellular imaging. Annu. Rev. Cell. Dev. Biol. 26, 285–314 (2010).

    Article  CAS  PubMed  Google Scholar 

  138. Shu, X. et al. A genetically encoded tag for correlated light and electron microscopy of intact cells, tissues, and organisms. PLoS Biol. 9, e1001041 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Wollert, T., Wunder, C., Lippincott-Schwartz, J. & Hurley, J. H. Membrane scission by the ESCRT-III complex. Nature 458, 172–177 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank M. Mishima, A. E. Smith, and M. R. Uehara for critical comments on the manuscript. Research in the Gerlich laboratory has received funding from the European Community's Seventh Framework Programme FP7/2007-2013 under grant agreements n° 241548 (MitoSys) and n° 258068 (Systems Microscopy), a grant from the Swiss National Science Foundation (SNF), and by an EMBO long-term fellowship to J. P. Fededa.

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    Present address: Present address: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria,

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  1. Juan Pablo Fededa and Daniel W. Gerlich: Institute of Biochemistry, Swiss Federal Institute of Technology Zurich, CH-8093 Zurich, Switzerland,

    Juan Pablo Fededa & Daniel W. Gerlich

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Fededa, J., Gerlich, D. Molecular control of animal cell cytokinesis. Nat Cell Biol 14, 440–447 (2012). https://doi.org/10.1038/ncb2482

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