Polar actomyosin contractility destabilizes the position of the cytokinetic furrow

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Abstract

Cytokinesis, the physical separation of daughter cells at the end of mitosis, requires precise regulation of the mechanical properties of the cell periphery1,2. Although studies of cytokinetic mechanics mostly focus on the equatorial constriction ring3, a contractile actomyosin cortex is also present at the poles of dividing cells2,4. Whether polar forces influence cytokinetic cell shape and furrow positioning remains an open question. Here we demonstrate that the polar cortex makes cytokinesis inherently unstable. We show that limited asymmetric polar contractions occur during cytokinesis, and that perturbing the polar cortex leads to cell shape oscillations, resulting in furrow displacement and aneuploidy. A theoretical model based on a competition between cortex turnover and contraction dynamics accurately accounts for the oscillations. We further propose that membrane blebs, which commonly form at the poles of dividing cells5 and whose role in cytokinesis has long been enigmatic, stabilize cell shape by acting as valves releasing cortical contractility. Our findings reveal an inherent instability in the shape of the dividing cell and unveil a novel, spindle-independent mechanism ensuring the stability of cleavage furrow positioning.

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Figure 1: The shape of the cleaving cell displays inherent shape instabilities.
Figure 2: Perturbation of the polar cortex enhances cytokinetic shape instabilities.
Figure 3: Dynamic characterization and model of shape oscillations.
Figure 4: Cell shape stability during cytokinesis.

Change history

  • 25 August 2011

    Fig. 3e axis label was corrected.

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Acknowledgements

We thank J. S. Bois, A. G. Clark, S. W. Grill, C. P. Heisenberg, J. Howard, A. A. Hyman, J. F. Joanny, D. K. Lubensky, A. Oates, M. Piel, I. M. Tolic-Norrelykke, W. Zachariae and M. Zerial for discussions and comments on the manuscript, and J. Roensch and the Max Planck Institute of Molecular Cell Biology and Genetics Light Microscopy Facility for technical assistance. This work was supported by the Polish Ministry of Science and Higher Education and by the Max Planck Society.

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Authors

Contributions

J.S., M.B., G.S. and E.P. designed the research and wrote the paper; J.S. performed the experiments except the local drug delivery; M.B. developed the image analysis tools; J.S., M.B. and G.S. analysed the data; A.O. and J.-Y.T. designed and performed the local drug-delivery experiments; G.S. developed the theoretical model.

Corresponding author

Correspondence to Ewa Paluch.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Texts 1-5 for the theoretical model, a Supplementary Discussion, additional references, Supplementary Figures 1-14 with legends, Supplementary Table 1 and legends for Supplementary Movies 1-11. (PDF 9983 kb)

Supplementary Movie 1

This movie shows bleb formation during cytokinesis (see Supplementary Information file for full legend). (MOV 8655 kb)

Supplementary Movie 2

In this movie we see cytoplasmic flows in control dividing cell (see Supplementary Information file for full legend). (MOV 2405 kb)

Supplementary Movie 3

This movie shows that large amplitude cell shape oscillations lead to cytokinesis failure (see Supplementary Information file for full legend). (MOV 381 kb)

Supplementary Movie 4

This movie shows large amplitude cell shape oscillations upon spindle depolymerisation (see Supplementary Information file for full legend). (MOV 2264 kb)

Supplementary Movie 5

This movie shows the adhesion of a cell to the substrate during division (see Supplementary Information file for full legend). (MOV 7989 kb)

Supplementary Movie 6

This movie shows that local actin depolymerisation leads to assymetric contractility and cell shape oscillations (see Supplementary Information file for full legend). (MOV 139 kb)

Supplementary Movie 7

This movie shows that the Laser ablation of the polar cortex leads to cell shape oscillations and cytokinesis failure. (MOV 877 kb)

Supplementary Movie 8

This movie shows that anillin depletion leads to cell shape oscillations and cytokinesis failure (see Supplementary Information file for full legend). (MOV 10637 kb)

Supplementary Movie 9

In this movie we see that the laser ablation of the equatorial cortex in L929 fibroblast leads to periodic cortical disassembly-assembly cycles and cell shape oscillations (see Supplementary Information file for full legend). (MOV 4172 kb)

Supplementary Movie 10

In this movie we see that the bleb induction in the contracting pole during cell shape oscillations causes premature reversal of the direction of the cytoplasmic flow (see Supplementary Information file for full legend). (MOV 877 kb)

Supplementary Movie 11

This movie shows shape oscillations induced by global stabilisation of the acto-myosin cortex by lectin crosslinking (see Supplementary Information file for full legend). (MOV 851 kb)

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Sedzinski, J., Biro, M., Oswald, A. et al. Polar actomyosin contractility destabilizes the position of the cytokinetic furrow. Nature 476, 462–466 (2011). https://doi.org/10.1038/nature10286

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