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Coupling changes in cell shape to chromosome segregation

Nature Reviews Molecular Cell Biology volume 17, pages 511–521 (2016)Cite this article

Subjects

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.

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Figure 1: Cell shape changes during mitosis.
Figure 2: Cortical actomyosin network reorganization during mitotic rounding.
Figure 3: Forces experienced by the cells during mitotic rounding.
Figure 4: Polar relaxation and coupling of chromosome segregation to cytokinesis.
Figure 5: Structural changes at mitotic exit.

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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.

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  1. MRC Laboratory of Molecular Cell Biology, University College London, Gower Street, London, WC1E 6BT, UK

    Nitya Ramkumar & Buzz Baum

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  1. Nitya Ramkumar
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Correspondence to Buzz Baum.

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PowerPoint slides

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.

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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

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