Abstract
During the final stage of cell division, the future daughter cells are physically separated through abscission. This process requires coordination of many molecular machines, including endocytic and secretory vesicle trafficking proteins as well as ESCRT (endosomal sorting complex required for transport) proteins, that mediate a complex series of events to culminate in the final separation of daughter cells. Abscission is coordinated with other cellular processes (for example, nuclear pore reassembly) through mitotic kinases such as Aurora B and Polo-like kinase 1, which act as master regulators to ensure proper progression of abscission.
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References
Eggert, U. S., Mitchison, T. J. & Field, C. M. Animal cytokinesis: from parts list to mechanisms. Annu. Rev. Biochem. 75, 543–566 (2006).
Skop, A. R., Liu, H., Yates, J. 3rd, Meyer, B. J. & Heald, R. Dissection of the mammalian midbody proteome reveals conserved cytokinesis mechanisms. Science 305, 61–66 (2004).
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).
Guizetti, J. et al. Cortical constriction during abscission involves helices of ESCRT-III-dependent filaments. Science 331, 1616–1620 (2011).
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).
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).
Elad, N., Abramovitch, S., Sabanay, H. & Medalia, O. Microtubule organization in the final stages of cytokinesis as revealed by cryo-electron tomography. J. Cell Sci. 124, 207–215 (2011).
Schluter, M. A. et al. Trafficking of Crumbs3 during cytokinesis is crucial for lumen formation. Mol. Biol. Cell 20, 4652–4663 (2009).
Hehnly, H. & Doxsey, S. Polarity sets the stage for cytokinesis. Mol. Biol. Cell 23, 7–11 (2012).
Carlton, J. G. & Martin-Serrano, J. Parallels between cytokinesis and retroviral budding: a role for the ESCRT machinery. Science 316, 1908–1912 (2007).
Yang, D. et al. Structural basis for midbody targeting of spastin by the ESCRT-III protein CHMP1B. Nature Struct. Mol. Biol. 15, 1278–1286 (2008).
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).
Steigemann, P. et al. Aurora B-mediated abscission checkpoint protects against tetraploidization. Cell 136, 473–484 (2009).
Mackay, D. R., Elgort, S. W. & Ullman, K. S. The nucleoporin Nup153 has separable roles in both early mitotic progression and the resolution of mitosis. Mol. Biol. Cell 20, 1652–1660 (2009).
Platani, M. et al. The Nup107–160 nucleoporin complex promotes mitotic events via control of the localization state of the chromosome passenger complex. Mol. Biol. Cell 20, 5260–5275 (2009).
Carlton, J. G., Caballe, A., Agromayor, M., Kloc, M. & Martin-Serrano, J. ESCRT-III governs the Aurora B-mediated abscission checkpoint through CHMP4C. Science 336, 220–225 (2012).
Wilson, G. M. et al. The FIP3–Rab11 protein complex regulates recycling endosome targeting to the cleavage furrow during late cytokinesis. Mol. Biol. Cell 16, 849–860 (2005).
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).
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).
Cascone, I. et al. Distinct roles of RalA and RalB in the progression of cytokinesis are supported by distinct RalGEFs. EMBO J. 27, 2375–2387 (2008).
Zhao, W. M., Seki, A. & Fang, G. Cep55, a microtubule-bundling protein, associates with centralspindlin to control the midbody integrity and cell abscission during cytokinesis. Mol. Biol. Cell 17, 3881–3896 (2006).
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).
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).
Chesneau, L. et al. An ARF6/Rab35 GTPase cascade for endocytic recycling and successful cytokinesis. Curr. Biol. 22, 147–153 (2012).
Schiel, J. A. et al. Endocytic membrane fusion and buckling-induced microtubule severing mediate cell abscission. J. Cell Sci. 124, 1411–1424 (2011).
Finger, F. P. Reining in cytokinesis with a septin corral. Bioessays 27, 5–8 (2005).
Dambournet, D. et al. Rab35 GTPase and OCRL phosphatase remodel lipids and F-actin for successful cytokinesis. Nature Cell Biol. 13, 981–988 (2011).
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).
Martin-Belmonte, F. & Mostov, K. Phosphoinositides control epithelial development. Cell Cycle 6, 1957–1961 (2007).
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).
Wu, S., Mehta, S. Q., Pichaud, F., Bellen, H. J. & Quiocho, F. A. Sec15 interacts with Rab11 via a novel domain and affects Rab11 localization in vivo. Nature Struct. Mol. Biol. 12, 879–885 (2005).
Henry, L. & Sheff, D. R. Rab8 regulates basolateral secretory, but not recycling, traffic at the recycling endosome. Mol. Biol. Cell 19, 2059–2068 (2008).
Kaplan, A. & Reiner, O. Linking cytoplasmic dynein and transport of Rab8 vesicles to the midbody during cytokinesis by the doublecortin domain-containing 5 protein. J. Cell Sci. 124, 3989–4000 (2011).
Mellman, I. & Nelson, W. J. Coordinated protein sorting, targeting and distribution in polarized cells. Nature Rev. Mol. Cell Biol. 9, 833–845 (2008).
Balklava, Z., Pant, S., Fares, H. & Grant, B. D. Genome-wide analysis identifies a general requirement for polarity proteins in endocytic traffic. Nature Cell Biol. 9, 1066–1073 (2007).
Wollert, T. et al. The ESCRT machinery at a glance. J. Cell Sci. 122, 2163–2166 (2009).
Henne, W. M., Buchkovich, N. J. & Emr, S. D. The ESCRT pathway. Dev. Cell 21, 77–91 (2011).
Caballe, A. & Martin-Serrano, J. ESCRT machinery and cytokinesis: the road to daughter cell separation. Traffic 12, 1318–1326 (2011).
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).
Lee, H. H., Elia, N., Ghirlando, R., Lippincott-Schwartz, J. & Hurley, J. H. Midbody targeting of the ESCRT machinery by a noncanonical coiled coil in CEP55. Science 322, 576–580 (2008).
Pohl, C. & Jentsch, S. Final stages of cytokinesis and midbody ring formation are controlled by BRUCE. Cell 132, 832–845 (2008).
Agromayor, M. et al. Essential role of hIST1 in cytokinesis. Mol. Biol. Cell 20, 1374–1387 (2009).
Jouvenet, N., Zhadina, M., Bieniasz, P. D. & Simon, S. M. Dynamics of ESCRT protein recruitment during retroviral assembly. Nature Cell Biol. 13, 394–401 (2011).
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).
Lambert, C., Doring, T. & Prange, R. Hepatitis B virus maturation is sensitive to functional inhibition of ESCRT-III, Vps4, and γ2-adaptin. J. Virol. 81, 9050–9060 (2007).
Hanson, P. I., Roth, R., Lin, Y. & Heuser, J. E. Plasma membrane deformation by circular arrays of ESCRT-III protein filaments. J. Cell Biol. 180, 389–402 (2008).
Ghazi-Tabatabai, S. et al. Structure and disassembly of filaments formed by the ESCRT-III subunit Vps24. Structure 16, 1345–1356 (2008).
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).
Petronczki, M., Lenart, P. & Peters, J. M. Polo on the rise-from mitotic entry to cytokinesis with Plk1. Dev. Cell 14, 646–659 (2008).
Carmena, M., Ruchaud, S. & Earnshaw, W. C. Making the Auroras glow: regulation of Aurora A and B kinase function by interacting proteins. Curr. Opin. Cell Biol. 21, 796–805 (2009).
Fabbro, M. et al. Cdk1/Erk2- and Plk1-dependent phosphorylation of a centrosome protein, Cep55, is required for its recruitment to midbody and cytokinesis. Dev. Cell 9, 477–488 (2005).
Lindon, C. & Pines, J. Ordered proteolysis in anaphase inactivates Plk1 to contribute to proper mitotic exit in human cells. J. Cell Biol. 164, 233–241 (2004).
Capalbo, L. et al. The chromosomal passenger complex controls the function of endosomal sorting complex required for transport-III Snf7 proteins during cytokinesis. Open Biol. 2, 120070 (2012).
D'Angelo, M. A. & Hetzer, M. W. Structure, dynamics and function of nuclear pore complexes. Trends Cell Biol. 18, 456–466 (2008).
Robinson, D. N., Girard, K. D., Octtaviani, E. & Reichl, E. M. Dictyostelium cytokinesis: from molecules to mechanics. J. Muscle Res. Cell. Motil. 23, 719–727 (2002).
Jurgens, G. Plant cytokinesis: fission by fusion. Trends Cell Biol. 15, 277–283 (2005).
Burch-Smith, T. M. & Zambryski, P. C. Plasmodesmata paradigm shift: regulation from without versus within. Annu. Rev. Plant Biol. 63, 239–260 (2012).
Rosa, J., Canovas, P., Islam, A., Altieri, D. C. & Doxsey, S. J. Survivin modulates microtubule dynamics and nucleation throughout the cell cycle. Mol. Biol. Cell 17, 1483–1493 (2006).
Janke, C. & Bulinski, J. C. Post-translational regulation of the microtubule cytoskeleton: mechanisms and functions. Nature Rev. Mol. Cell Biol. 12, 773–786 (2011).
Acknowledgements
The authors apologize to colleagues whose work is not discussed or cited owing to space constraints. The authors are particularly grateful to A. Bright and S. Redick from the Doxsey laboratory for critical reading of the manuscript and thoughtful discussions. Work in the Doxsey laboratory is supported by the US National Institutes of Health (NIH), the Ellison Medical Foundation, the W. M. Keck Foundation and the US Department of Defense.
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Chen, CT., Hehnly, H. & Doxsey, S. Orchestrating vesicle transport, ESCRTs and kinase surveillance during abscission. Nat Rev Mol Cell Biol 13, 483–488 (2012). https://doi.org/10.1038/nrm3395
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DOI: https://doi.org/10.1038/nrm3395
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