Key Points
-
Animal cells undergo dramatic changes in their shape as they progress through mitosis and division. This process begins with rounding soon after cells enter mitosis.
-
Mitotic rounding is an active process that depends on a combination of de-adhesion, actomyosin-based contraction and osmotic swelling.
-
Adhesion remodelling is essential for normal cell rounding during mitosis and is triggered by inactivation of the small GTPase RAP1.
-
Entry into mitosis triggers a dramatic change in actin organization and dynamics, leading to the assembly of a formin-based actomyosin network that is tethered to the overlying membrane by activated ERM (Ezrin, Radixin, Moesin) proteins.
-
The changes in actin organization and cell shape that accompany mitotic exit are driven by a combination of actomyosin ring assembly and polar relaxation, which can be induced by chromatin-based signals.
-
Whereas remodelling of the actin and microtubule cytoskeletons seems to be relatively independent during mitotic entry, spindle elongation and cytokinesis must be tightly coupled in space and time to ensure precise cell division.
Abstract
Animal cells undergo dramatic changes in shape, mechanics and polarity as they progress through the different stages of cell division. These changes begin at mitotic entry, with cell–substrate adhesion remodelling, assembly of a cortical actomyosin network and osmotic swelling, which together enable cells to adopt a near spherical form even when growing in a crowded tissue environment. These shape changes, which probably aid spindle assembly and positioning, are then reversed at mitotic exit to restore the interphase cell morphology. Here, we discuss the dynamics, regulation and function of these processes, and how cell shape changes and sister chromatid segregation are coupled to ensure that the daughter cells generated through division receive their fair inheritance.
Similar content being viewed by others
References
Jongsma, M. L., Berlin, I. & Neefjes, J. On the move: organelle dynamics during mitosis. Trends Cell Biol. 25, 112–124 (2015).
Balasubramanian, M. K., Srinivasan, R., Huang, Y. & Ng, K. H. Comparing contractile apparatus-driven cytokinesis mechanisms across kingdoms. Cytoskeleton 69, 942–956 (2012).
Mercier, R., Kawai, Y. & Errington, J. General principles for the formation and proliferation of a wall-free (L-form) state in bacteria. eLife 3, e04629 (2014).
Nestor-Bergmann, A., Goddard, G. & Woolner, S. Force and the spindle: mechanical cues in mitotic spindle orientation. Semin. Cell Dev. Biol. 34, 133–139 (2014).
Fink, J. et al. External forces control mitotic spindle positioning. Nat. Cell Biol. 13, 771–778 (2011).
Stout, J. R., Rizk, R. S., Kline, S. L. & Walczak, C. E. Deciphering protein function during mitosis in PtK cells using RNAi. BMC Cell Biol. 7, 26 (2006).
Woolner, S. & Papalopulu, N. Spindle position in symmetric cell divisions during epiboly is controlled by opposing and dynamic apicobasal forces. Dev. Cell 22, 775–787 (2012).
Zang, J. H. et al. On the role of myosin-II in cytokinesis: division of Dictyostelium cells under adhesive and nonadhesive conditions. Mol. Biol. Cell 8, 2617–2629 (1997).
Lancaster, O. M. et al. Mitotic rounding alters cell geometry to ensure efficient bipolar spindle formation. Dev. Cell 25, 270–283 (2013). This study shows that mitotic rounding (rather than the actin cytoskeleton) is important for spindle formation.
Strzyz, P. J. et al. Interkinetic nuclear migration is centrosome independent and ensures apical cell division to maintain tissue integrity. Dev. Cell 32, 203–219 (2015).
Wyatt, T. P. et al. Emergence of homeostatic epithelial packing and stress dissipation through divisions oriented along the long cell axis. Proc. Natl Acad. Sci. USA 112, 5726–5731 (2015).
Dao, V. T., Dupuy, A. G., Gavet, O., Caron, E. & de Gunzburg, J. Dynamic changes in Rap1 activity are required for cell retraction and spreading during mitosis. J. Cell Sci. 122, 2996–3004 (2009). This study identifies RAP1 as a key regulator of mitotic adhesion remodelling.
Matthews, H. K. et al. Changes in Ect2 localization couple actomyosin-dependent cell shape changes to mitotic progression. Dev. Cell 23, 371–383 (2012). This study identifies ECT2 as a master regulator of cell shape changes, during both entry into and exit from mitosis.
Rosa, A., Vlassaks, E., Pichaud, F. & Baum, B. Ect2/Pbl acts via Rho and polarity proteins to direct the assembly of an isotropic actomyosin cortex upon mitotic entry. Dev. Cell 32, 604–616 (2015).
Gavet, O. & Pines, J. Progressive activation of CyclinB1-Cdk1 coordinates entry to mitosis. Dev. Cell 18, 533–543 (2010).
Solomon, M. J., Glotzer, M., Lee, T. H., Philippe, M. & Kirschner, M. W. Cyclin activation of p34cdc2. Cell 63, 1013–1024 (1990).
Pomerening, J. R., Sontag, E. D. & Ferrell, J. E. Jr. Building a cell cycle oscillator: hysteresis and bistability in the activation of Cdc2. Nat. Cell Biol. 5, 346–351 (2003).
Pomerening, J. R., Kim, S. Y. & Ferrell, J. E. Jr. Systems-level dissection of the cell-cycle oscillator: bypassing positive feedback produces damped oscillations. Cell 122, 565–578 (2005).
Robertson, J. et al. Defining the phospho-adhesome through the phosphoproteomic analysis of integrin signalling. Nat. Commun. 6, 6265 (2015).
Marchesi, S. et al. DEPDC1B coordinates de-adhesion events and cell-cycle progression at mitosis. Dev. Cell 31, 420–433 (2014).
Nigg, E. A. The substrates of the cdc2 kinase. Semin. Cell Biol. 2, 261–270 (1991).
Curtis, M., Nikolopoulos, S. N. & Turner, C. E. Actopaxin is phosphorylated during mitosis and is a substrate for cyclin B1/cdc2 kinase. Biochem. J. 363, 233–242 (2002).
Olsen, J. V. et al. Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. 3, ra3 (2010).
Suzuki, K. & Takahashi, K. Reduced cell adhesion during mitosis by threonine phosphorylation of β1 integrin. J. Cell. Physiol. 197, 297–305 (2003).
Yamakita, Y. et al. Dissociation of FAK/p130CAS/c-Src complex during mitosis: role of mitosis-specific serine phosphorylation of FAK. J. Cell Biol. 144, 315–324 (1999).
Cramer, L. P. & Mitchison, T. J. Investigation of the mechanism of retraction of the cell margin and rearward flow of nodules during mitotic cell rounding. Mol. Biol. Cell 8, 109–119 (1997). This study was one of the few to study the formation of retraction fibres during mitotic rounding.
Toyoshima, F. & Nishida, E. Integrin-mediated adhesion orients the spindle parallel to the substratum in an EB1- and myosin X-dependent manner. EMBO J. 26, 1487–1498 (2007).
Mali, P., Wirtz, D. & Searson, P. C. Interplay of RhoA and motility in the programmed spreading of daughter cells postmitosis. Biophys. J. 99, 3526–3534 (2010).
Ferreira, J. G., Pereira, A. J., Akhmanova, A. & Maiato, H. Aurora B spatially regulates EB3 phosphorylation to coordinate daughter cell adhesion with cytokinesis. J. Cell Biol. 201, 709–724 (2013).
Bellis, J. et al. The tumor suppressor Apc controls planar cell polarities central to gut homeostasis. J. Cell Biol. 198, 331–341 (2012).
Kosodo, Y. et al. Cytokinesis of neuroepithelial cells can divide their basal process before anaphase. EMBO J. 27, 3151–3163 (2008).
Reinsch, S. & Karsenti, E. Orientation of spindle axis and distribution of plasma membrane proteins during cell division in polarized MDCKII cells. J. Cell Biol. 126, 1509–1526 (1994).
Lecuit, T. & Wieschaus, E. Junctions as organizing centers in epithelial cells? A fly perspective. Traffic 3, 92–97 (2002).
Clark, A. G., Dierkes, K. & Paluch, E. K. Monitoring actin cortex thickness in live cells. Biophys. J. 105, 570–580 (2013).
Bovellan, M. et al. Cellular control of cortical actin nucleation. Curr. Biol. 24, 1628–1635 (2014). This study identifies roles for different actin regulators in cortical actin network formation.
Castanon, I. et al. Anthrax toxin receptor 2a controls mitotic spindle positioning. Nat. Cell Biol. 15, 28–39 (2013).
Ibarra, N., Pollitt, A. & Insall, R. H. Regulation of actin assembly by SCAR/WAVE proteins. Biochem. Soc. Trans. 33, 1243–1246 (2005).
Davidson, A. J., Ura, S., Thomason, P. A., Kalna, G. & Insall, R. H. Abi is required for modulation and stability but not localization or activation of the SCAR/WAVE complex. Eukaryot. Cell 12, 1509–1516 (2013).
Zhuang, C. et al. CDK1-mediated phosphorylation of Abi1 attenuates Bcr-Abl-induced F-actin assembly and tyrosine phosphorylation of WAVE complex during mitosis. J. Biol. Chem. 286, 38614–38626 (2011).
Skau, C. T., Neidt, E. M. & Kovar, D. R. Role of tropomyosin in formin-mediated contractile ring assembly in fission yeast. Mol. Biol. Cell 20, 2160–2173 (2009).
Miki, T., Smith, C. L., Long, J. E., Eva, A. & Fleming, T. P. Oncogene ect2 is related to regulators of small GTP-binding proteins. Nature 362, 462–465 (1993).
Maddox, A. S. & Burridge, K. RhoA is required for cortical retraction and rigidity during mitotic cell rounding. J. Cell Biol. 160, 255–265 (2003). This study identifies RhoA as a key regulator of mitotic rounding.
Yuce, O., Piekny, A. & Glotzer, M. An ECT2–centralspindlin complex regulates the localization and function of RhoA. J. Cell Biol. 170, 571–582 (2005).
Watanabe, N., Kato, T., Fujita, A., Ishizaki, T. & Narumiya, S. Cooperation between mDia1 and ROCK in Rho-induced actin reorganization. Nat. Cell Biol. 1, 136–143 (1999).
Oceguera-Yanez, F. et al. Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis. J. Cell Biol. 168, 221–232 (2005).
Motegi, F. & Sugimoto, A. Sequential functioning of the ECT-2 RhoGEF, RHO-1 and CDC-42 establishes cell polarity in Caenorhabditis elegans embryos. Nat. Cell Biol. 8, 978–985 (2006).
Field, C. M. et al. Actin behavior in bulk cytoplasm is cell cycle regulated in early vertebrate embryos. J. Cell Sci. 124, 2086–2095 (2011). This study shows how cell cycle state influences actin dynamics.
Ritchey, L. & Chakrabarti, R. Aurora A kinase modulates actin cytoskeleton through phosphorylation of Cofilin: implication in the mitotic process. Biochim. Biophys. Acta 1843, 2719–2729 (2014).
Takahashi, H., Funakoshi, H. & Nakamura, T. LIM-kinase as a regulator of actin dynamics in spermatogenesis. Cytogenet. Genome Res. 103, 290–298 (2003).
Kuilman, T. et al. Identification of Cdk targets that control cytokinesis. EMBO J. 34, 81–96 (2015).
Carreno, S. et al. Moesin and its activating kinase Slik are required for cortical stability and microtubule organization in mitotic cells. J. Cell Biol. 180, 739–746 (2008).
Kunda, P., Pelling, A. E., Liu, T. & Baum, B. Moesin controls cortical rigidity, cell rounding, and spindle morphogenesis during mitosis. Curr. Biol. 18, 91–101 (2008). References 51 and 52 identify roles for active ERM proteins in the assembly of the mitotic cortex.
Li, Q. et al. Self-masking in an intact ERM-merlin protein: an active role for the central α-helical domain. J. Mol. Biol. 365, 1446–1459 (2007).
Roubinet, C. et al. Molecular networks linked by Moesin drive remodeling of the cell cortex during mitosis. J. Cell Biol. 195, 99–112 (2011).
Janetopoulos, C. & Devreotes, P. Phosphoinositide signaling plays a key role in cytokinesis. J. Cell Biol. 174, 485–490 (2006).
Maniti, O. et al. Binding of moesin and ezrin to membranes containing phosphatidylinositol (4,5) bisphosphate: a comparative study of the affinity constants and conformational changes. Biochim. Biophys. Acta 1818, 2839–2849 (2012).
Zhai, Y., Kronebusch, P. J., Simon, P. M. & Borisy, G. G. Microtubule dynamics at the G2/M transition: abrupt breakdown of cytoplasmic microtubules at nuclear envelope breakdown and implications for spindle morphogenesis. J. Cell Biol. 135, 201–214 (1996).
Clarke, P. R. & Zhang, C. Spatial and temporal coordination of mitosis by Ran GTPase. Nat. Rev. Mol. Cell Biol. 9, 464–477 (2008).
Stewart, M. P. et al. Hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding. Nature 469, 226–230 (2011). This study was the first to propose a role for changes in osmotic pressure in generating the forces accompanying mitotic rounding.
Son, S. et al. Resonant microchannel volume and mass measurements show that suspended cells swell during mitosis. J. Cell Biol. 211, 757–763 (2015).
Zlotek-Zlotkiewicz, E., Monnier, S., Cappello, G., Le Berre, M. & Piel, M. Optical volume and mass measurements show that mammalian cells swell during mitosis. J. Cell Biol. 211, 765–774 (2015). This study shows that cells swell as they enter mitosis.
Cattin, C. J. et al. Mechanical control of mitotic progression in single animal cells. Proc. Natl Acad. Sci. USA 112, 11258–11263 (2015).
Sorce, B. et al. Mitotic cells contract actomyosin cortex and generate pressure to round against or escape epithelial confinement. Nat. Commun. 6, 8872 (2015).
Ramanathan, S. P. et al. Cdk1-dependent mitotic enrichment of cortical myosin II promotes cell rounding against confinement. Nat. Cell Biol. 17, 148–159 (2015).
Fischer-Friedrich, E., Hyman, A. A., Julicher, F., Muller, D. J. & Helenius, J. Quantification of surface tension and internal pressure generated by single mitotic cells. Sci. Rep. 4, 6213 (2014).
Hoijman, E., Rubbini, D., Colombelli, J. & Alsina, B. Mitotic cell rounding and epithelial thinning regulate lumen growth and shape. Nat. Commun. 6, 7355 (2015).
Kondo, T. & Hayashi, S. Mitotic cell rounding accelerates epithelial invagination. Nature 494, 125–129 (2013). This study shows how the forces generated by mitotic rounding can buckle a tissue.
McCarthy Campbell, E. K., Werts, A. D. & Goldstein, B. A cell cycle timer for asymmetric spindle positioning. PLoS Biol. 7, e1000088 (2009).
Echard, A. & O'Farrell, P. H. The degradation of two mitotic cyclins contributes to the timing of cytokinesis. Curr. Biol. 13, 373–383 (2003).
Mossaid, I. & Fahrenkrog, B. Complex commingling: nucleoporins and the spindle assembly checkpoint. Cells 4, 706–725 (2015).
Doncic, A., Ben-Jacob, E. & Barkai, N. Evaluating putative mechanisms of the mitotic spindle checkpoint. Proc. Natl Acad. Sci. USA 102, 6332–6337 (2005).
Foley, E. A. & Kapoor, T. M. Microtubule attachment and spindle assembly checkpoint signalling at the kinetochore. Nat. Rev. Mol. Cell Biol. 14, 25–37 (2013).
Chang, L. & Barford, D. Insights into the anaphase-promoting complex: a molecular machine that regulates mitosis. Curr. Opin. Struct. Biol. 29, 1–9 (2014).
Nasmyth, K. Cohesin: a catenase with separate entry and exit gates? Nat. Cell Biol. 13, 1170–1177 (2011).
Sivakumar, S. & Gorbsky, G. J. Spatiotemporal regulation of the anaphase-promoting complex in mitosis. Nat. Rev. Mol. Cell Biol. 16, 82–94 (2015).
Fededa, J. P. & Gerlich, D. W. Molecular control of animal cell cytokinesis. Nat. Cell Biol. 14, 440–447 (2012).
Schellhaus, A. K., De Magistris, P. & Antonin, W. Nuclear reformation at the end of mitosis. J. Mol. Biol. 428, 1962–1985 (2015).
Field, C. M. & Alberts, B. M. Anillin, a contractile ring protein that cycles from the nucleus to the cell cortex. J. Cell Biol. 131, 165–178 (1995).
Green, R. A., Paluch, E. & Oegema, K. Cytokinesis in animal cells. Annu. Rev. Cell Dev. Biol. 28, 29–58 (2012).
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). This study shows how ECT2 is localized to the plasma membrane at the cell midzone at the onset of anaphase.
Kunda, P. et al. PP1-mediated moesin dephosphorylation couples polar relaxation to mitotic exit. Curr. Biol. 22, 231–236 (2012).
Mavrakis, M. et al. Septins promote F-actin ring formation by crosslinking actin filaments into curved bundles. Nat. Cell Biol. 16, 322–334 (2014).
Founounou, N., Loyer, N. & Le Borgne, R. Septins regulate the contractility of the actomyosin ring to enable adherens junction remodeling during cytokinesis of epithelial cells. Dev. Cell 24, 242–255 (2013).
Guillot, C. & Lecuit, T. Adhesion disengagement uncouples intrinsic and extrinsic forces to drive cytokinesis in epithelial tissues. Dev. Cell 24, 227–241 (2013).
Takeda, T. et al. Drosophila F-BAR protein Syndapin contributes to coupling the plasma membrane and contractile ring in cytokinesis. Open Biol. 3, 130081 (2013).
Roberts-Galbraith, R. H. et al. Dephosphorylation of F-BAR protein Cdc15 modulates its conformation and stimulates its scaffolding activity at the cell division site. Mol. Cell 39, 86–99 (2010).
Rappaport, R. Cytokinesis in Animal Cells (Cambridge Univ. Press, 1996). This book summarizes decades of cell division research.
Rosenblatt, J., Cramer, L. P., Baum, B. & McGee, K. M. Myosin II-dependent cortical movement is required for centrosome separation and positioning during mitotic spindle assembly. Cell 117, 361–372 (2004).
De Simone, A., Nedelec, F. & Gonczy, P. Dynein transmits polarized actomyosin cortical flows to promote centrosome separation. Cell Rep. 14, 2250–2262 (2016).
Sawin, K. E. & Mitchison, T. J. Mitotic spindle assembly by two different pathways in vitro. J. Cell Biol. 112, 925–940 (1991).
Mitchison, T. et al. Growth, interaction, and positioning of microtubule asters in extremely large vertebrate embryo cells. Cytoskeleton 69, 738–750 (2012).
White, E. A. & Glotzer, M. Centralspindlin: at the heart of cytokinesis. Cytoskeleton 69, 882–892 (2012).
Piekny, A. J. & Glotzer, M. Anillin is a scaffold protein that links RhoA, actin, and myosin during cytokinesis. Curr. Biol. 18, 30–36 (2008).
Nguyen, P. A. et al. Spatial organization of cytokinesis signaling reconstituted in a cell-free system. Science 346, 244–247 (2014).
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).
Zhang, D. & Glotzer, M. The RhoGAP activity of CYK-4/MgcRacGAP functions non-canonically by promoting RhoA activation during cytokinesis. eLife 4, e08898 (2015).
Bastos, R. N., Penate, X., Bates, M., Hammond, D. & Barr, F. A. CYK4 inhibits Rac1-dependent PAK1 and ARHGEF7 effector pathways during cytokinesis. J. Cell Biol. 198, 865–880 (2012).
Logan, M. R. & Mandato, C. A. Regulation of the actin cytoskeleton by PIP2 in cytokinesis. Biol. Cell 98, 377–388 (2006).
Basant, A. et al. Aurora B kinase promotes cytokinesis by inducing centralspindlin oligomers that associate with the plasma membrane. Dev. Cell 33, 204–215 (2015).
Pacquelet, A., Uhart, P., Tassan, J. P. & Michaux, G. PAR-4 and anillin regulate myosin to coordinate spindle and furrow position during asymmetric division. J. Cell Biol. 210, 1085–1099 (2015).
Cabernard, C., Prehoda, K. E. & Doe, C. Q. A spindle-independent cleavage furrow positioning pathway. Nature 467, 91–94 (2010).
Ou, G., Stuurman, N., D'Ambrosio, M. & Vale, R. D. Polarized myosin produces unequal-size daughters during asymmetric cell division. Science 330, 677–680 (2010). These studies show that the position of the division plane is not always a simple consequence of spindle position.
Yeh, E. et al. Dynamic positioning of mitotic spindles in yeast: role of microtubule motors and cortical determinants. Mol. Biol. Cell 11, 3949–3961 (2000).
Charras, G. & Paluch, E. Blebs lead the way: how to migrate without lamellipodia. Nat. Rev. Mol. Cell Biol. 9, 730–736 (2008).
Sedzinski, J. et al. Polar actomyosin contractility destabilizes the position of the cytokinetic furrow. Nature 476, 462–466 (2011).
Rodrigues, N. T. et al. Kinetochore-localized PP1–Sds22 couples chromosome segregation to polar relaxation. Nature 524, 489–492 (2015). These studies investigate the regulation and function of anaphase polar relaxation.
Hickson, G. R., Echard, A. & O'Farrell, P. H. Rho-kinase controls cell shape changes during cytokinesis. Curr. Biol. 16, 359–370 (2006).
Wolpert, L. A relaxed modification of the Rappaport model for cytokinesis. J. Theor. Biol. 345, 109 (2014).
Canman, J. C. et al. Determining the position of the cell division plane. Nature 424, 1074–1078 (2003).
Hu, C. K., Coughlin, M., Field, C. M. & Mitchison, T. J. Cell polarization during monopolar cytokinesis. J. Cell Biol. 181, 195–202 (2008). This study explores how the cytokinesis machinery responds to forced mitotic exit in the absence of a bipolar spindle.
Kiyomitsu, T. & Cheeseman, I. M. Chromosome- and spindle-pole-derived signals generate an intrinsic code for spindle position and orientation. Nat. Cell Biol. 14, 311–317 (2012).
Kiyomitsu, T. & Cheeseman, I. M. Cortical dynein and asymmetric membrane elongation coordinately position the spindle in anaphase. Cell 154, 391–402 (2013).
Connell, M., Cabernard, C., Ricketson, D., Doe, C. Q. & Prehoda, K. E. Asymmetric cortical extension shifts cleavage furrow position in Drosophila neuroblasts. Mol. Biol. Cell 22, 4220–4226 (2011).
Bird, S. L., Heald, R. & Weis, K. RanGTP and CLASP1 cooperate to position the mitotic spindle. Mol. Biol. Cell 24, 2506–2514 (2013).
Silverman-Gavrila, R. V., Hales, K. G. & Wilde, A. Anillin-mediated targeting of peanut to pseudocleavage furrows is regulated by the GTPase Ran. Mol. Biol. Cell 19, 3735–3744 (2008).
Dehapiot, B. & Halet, G. Ran GTPase promotes oocyte polarization by regulating ERM (Ezrin/Radixin/Moesin) inactivation. Cell Cycle 12, 1672–1678 (2013).
Ohkura, H. & Yanagida, M. S. pombe gene sds22+ essential for a midmitotic transition encodes a leucine-rich repeat protein that positively modulates protein phosphatase-1. Cell 64, 149–157 (1991).
Grusche, F. A. et al. Sds22, a PP1 phosphatase regulatory subunit, regulates epithelial cell polarity and shape [Sds22 in epithelial morphology]. BMC Dev. Biol. 9, 14 (2009).
Wurzenberger, C. & Gerlich, D. W. Phosphatases: providing safe passage through mitotic exit. Nat. Rev. Mol. Cell Biol. 12, 469–482 (2011).
Lesage, B., Qian, J. & Bollen, M. Spindle checkpoint silencing: PP1 tips the balance. Curr. Biol. 21, R898–R903 (2011).
Petronczki, M., Lenart, P. & Peters, J. M. Polo on the rise — from mitotic entry to cytokinesis with Plk1. Dev. Cell 14, 646–659 (2008).
Kitagawa, M. & Lee, S. H. The chromosomal passenger complex (CPC) as a key orchestrator of orderly mitotic exit and cytokinesis. Front. Cell Dev. Biol. 3, 14 (2015).
Herszterg, S., Leibfried, A., Bosveld, F., Martin, C. & Bellaiche, Y. Interplay between the dividing cell and its neighbors regulates adherens junction formation during cytokinesis in epithelial tissue. Dev. Cell 24, 256–270 (2013). This study asks how cell division is organized to generate a new cell–cell interface following division in a tissue.
Morais-de-Sa, E. & Sunkel, C. E. Connecting polarized cytokinesis to epithelial architecture. Cell Cycle 12, 3583–3584 (2013).
Mitsushima, M. et al. Revolving movement of a dynamic cluster of actin filaments during mitosis. J. Cell Biol. 191, 453–462 (2010).
Neto, H., Collins, L. L. & Gould, G. W. Vesicle trafficking and membrane remodelling in cytokinesis. Biochem. J. 437, 13–24 (2011).
Lafaurie-Janvore, J. et al. ESCRT-III assembly and cytokinetic abscission are induced by tension release in the intercellular bridge. Science 339, 1625–1629 (2013).
Simon, G. C. et al. Sequential Cyk-4 binding to ECT2 and FIP3 regulates cleavage furrow ingression and abscission during cytokinesis. EMBO J. 27, 1791–1803 (2008).
Chalamalasetty, R. B., Hummer, S., Nigg, E. A. & Sillje, H. H. Influence of human Ect2 depletion and overexpression on cleavage furrow formation and abscission. J. Cell Sci. 119, 3008–3019 (2006).
Dambournet, D. et al. Rab35 GTPase and OCRL phosphatase remodel lipids and F-actin for successful cytokinesis. Nat. Cell Biol. 13, 981–988 (2011).
Manukyan, A., Ludwig, K., Sanchez-Manchinelly, S., Parsons, S. J. & Stukenberg, P. T. A complex of p190RhoGAP-A and anillin modulates RhoA-GTP and the cytokinetic furrow in human cells. J. Cell Sci. 128, 50–60 (2015).
Piel, M., Nordberg, J., Euteneuer, U. & Bornens, M. Centrosome-dependent exit of cytokinesis in animal cells. Science 291, 1550–1553 (2001).
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).
Mierzwa, B. & Gerlich, D. W. Cytokinetic abscission: molecular mechanisms and temporal control. Dev. Cell 31, 525–538 (2014).
Steigemann, P. et al. Aurora B-mediated abscission checkpoint protects against tetraploidization. Cell 136, 473–484 (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).
Olmos, Y., Hodgson, L., Mantell, J., Verkade, P. & Carlton, J. G. ESCRT-III controls nuclear envelope reformation. Nature 522, 236–239 (2015).
Maiato, H., Afonso, O. & Matos, I. A chromosome separation checkpoint: a midzone Aurora B gradient mediates a chromosome separation checkpoint that regulates the anaphase-telophase transition. Bioessays 37, 257–266 (2015).
Floyd, S. et al. Spatiotemporal organization of Aurora-B by APC/CCdh1 after mitosis coordinates cell spreading through FHOD1. J. Cell Sci. 126, 2845–2856 (2013).
Ferreira, J. G., Pereira, A. J., Akhmanova, A. & Maiato, H. Aurora B spatially regulates EB3 phosphorylation to coordinate daughter cell adhesion with cytokinesis. J. Cell Biol. 201, 709–724 (2013).
Crasta, K. et al. DNA breaks and chromosome pulverization from errors in mitosis. Nature 482, 53–58 (2012).
Kressmann, S., Campos, C., Castanon, I., Furthauer, M. & Gonzalez-Gaitan, M. Directional Notch trafficking in Sara endosomes during asymmetric cell division in the spinal cord. Nat. Cell Biol. 17, 333–339 (2015).
Furthauer, M. & Gonzalez-Gaitan, M. Endocytosis and mitosis: a two-way relationship. Cell Cycle 8, 3311–3318 (2009).
Jajoo, R. et al. Accurate concentration control of mitochondria and nucleoids. Science 351, 169–172 (2016).
Bernander, R. Archaea and the cell cycle. Mol. Microbiol. 29, 955–961 (1998).
Mauser, J. F. & Prehoda, K. E. Inscuteable regulates the Pins-Mud spindle orientation pathway. PLoS ONE 7, e29611 (2012).
Siller, K. H. & Doe, C. Q. Lis1/dynactin regulates metaphase spindle orientation in Drosophila neuroblasts. Dev. Biol. 319, 1–9 (2008).
Zheng, Z. et al. Evidence for dynein and astral microtubule-mediated cortical release and transport of Gαi/LGN/NuMA complex in mitotic cells. Mol. Biol. Cell 24, 901–913 (2013).
Acknowledgements
The authors would like to thank members of the Baum laboratory and anonymous reviewers for their critical reading of the text. B.B. and N.R. thank Cancer Research UK for funding, and B.B. thanks the UK Biotechnology and Biological Sciences Research Council (BBSRC) and University College London for support.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Glossary
- Astral microtubules
-
A subpopulation of dynamic microtubules, which originate from the centrosomes but do not attach to the chromosomes. They are present only during mitosis.
- Retraction fibres
-
Actin-rich fibres retained by cells as they round up as they enter mitosis. These hold the cells in place and are thought to guide spindle orientation to determine the division axis.
- Adherens junctions
-
Protein complexes consisting of cadherins and catenin, which are involved in cell–cell junctions in epithelial and endothelial cells.
- Tight junctions
-
Cell–cell junctions, consisting of occludins, claudins and associated proteins, which bring membranes of adjacent cells into close proximity to form a permeability barrier. They are positioned apical to the adherens junctions in vertebrates and (as septate junctions) basal to adherens junctions in most invertebrate epithelia.
- ARP2/3 complex
-
A protein complex consisting of seven polypeptides (including actin-related protein 2 (ARP2) and ARP3), which regulates the nucleation of branched actin filament networks from the filament minus end.
- Formins
-
Proteins defined by the presence of a formin homology 2 (FH2) domain, which nucleate actin filaments from growing (plus) ends to generate parallel or antiparallel filaments that are a good substrate for non-muscle myosin II.
- Non-muscle myosin II
-
An ATP-dependent motor protein that forms large bipolar 'minifilaments'. In non-muscle cells, these both crosslink actin filaments and walk along actin filaments to drive network contraction.
- Importins
-
Protein complexes that transport proteins containing nuclear localization sequences (NLS) into the nucleus. The complex consists of importin-α and importin-β.
- Spindle assembly check point
-
The checkpoint that delays anaphase onset until chromosomes are properly attached to the metaphase spindle.
- Anaphase-promoting complex
-
(APC). An E3 ubiquitin ligase that targets specific cell cycle proteins for degradation by the 26S proteasome upon satisfaction of the spindle assembly checkpoint, to trigger the separation of sister chromatids and the transition to anaphase.
- Actomyosin contractile ring
-
A contractile structure composed of actin and myosin filaments that deforms the plasma membrane to drive cytokinesis.
- Centralspindilin complex
-
A protein complex that localizes to overlapping antiparallel microtubules in anaphase to recruit proteins that drive local actomyosin ring formation, so that closure of the ring bisects the spindle.
- Chromosomal passenger complex
-
(CPC). A protein complex consisting of kinase Aurora B and its regulatory subunits borealin, INCENP and survivin, which relocalize from kinetochores to overlapping antiparallel microtubules at the midzones of cells in anaphase, to regulate actomyosin ring formation and, later, abscission.
- Midbody
-
Also called a Flemming body, the midbody is a structure that connects the two daughter cells towards the end of cytokinesis. It controls abscission, a process that leads to the physical separation of the two daughter cells.
Rights and permissions
About this article
Cite this article
Ramkumar, N., Baum, B. Coupling changes in cell shape to chromosome segregation. Nat Rev Mol Cell Biol 17, 511–521 (2016). https://doi.org/10.1038/nrm.2016.75
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrm.2016.75
- Springer Nature Limited
This article is cited by
-
In mitosis integrins reduce adhesion to extracellular matrix and strengthen adhesion to adjacent cells
Nature Communications (2023)
-
The nuclear lamina couples mechanical forces to cell fate in the preimplantation embryo via actin organization
Nature Communications (2023)
-
CDK1–cyclin-B1-induced kindlin degradation drives focal adhesion disassembly at mitotic entry
Nature Cell Biology (2022)
-
Fine-tuning cell organelle dynamics during mitosis by small GTPases
Frontiers of Medicine (2022)
-
Modeling ATP-mediated endothelial cell elongation on line patterns
Biomechanics and Modeling in Mechanobiology (2022)