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The 3Ms of central spindle assembly: microtubules, motors and MAPs

Nature Reviews Molecular Cell Biology volume 10, pages 9–20 (2009)Cite this article

Key Points

  • The central spindle consists of a set of microtubule bundles in anaphase cells that overlap for a short region at their plus ends.

  • The central spindle regulates cleavage furrow formation and completion of cytokinesis.

  • The central spindle forms in anaphase as cells exit mitosis. In unperturbed cells, the central spindle forms from mitotic spindle microtubules.

  • Under appropriate conditions, a bipolar central spindle can form spontaneously from non-spindle microtubules, without a mitotic spindle template.

  • Central spindle microtubule bundles are highly stabilized.

  • The formation of the central spindle requires kinesin motor proteins, microtubule-associated proteins (MAPs) and protein kinases. The central components include centralspindlin (a complex that contains kinesin and Rho GTPase-activating protein subunits), the microtubule-bundling protein protein regulator of cytokinesis 1 (PRC1) and the chromosome passenger complex (CPC).

  • Several of the proteins that are required for central spindle assembly are inactivated by phosphorylation during metaphase, and activated during anaphase.

  • The precise mechanism of microtubule bundling that results in overlapping microtubule plus ends remains be determined.

  • Models of the interactions of motors, MAPs and microtubules provide useful insights into how stable microtubule overlap can be established and suggest that local regulation of microtubule dynamics might have an important role.

Abstract

During metaphase, sister chromatids are positioned at the midpoint of the microtubule-based mitotic spindle in preparation for their segregation. The onset of anaphase triggers inactivation of the key mitotic kinase cyclin-dependent kinase 1 (CDK1) and the polewards movement of sister chromatids. During anaphase, the mitotic spindle reorganizes in preparation for cytokinesis. Kinesin motor proteins and microtubule-associated proteins bundle the plus ends of interpolar microtubules and generate the central spindle, which regulates cleavage furrow initiation and the completion of cytokinesis. Complementary approaches, including cell biology, genetics and computational modelling, have provided new insights into the mechanism and regulation of central spindle assembly.

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Figure 1: Assembly of the central spindle.
Figure 2: Structural features of central spindle components.
Figure 3: Localization of central spindle components.
Figure 4: Microtubule bundling mechanisms.
Figure 5: A working model for central spindle assembly.

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Acknowledgements

I thank B. Wolfe, E. White and M. Mishima for comments on the manuscript and Z. Thakkar for assistance in producing the micrographs. I thank C. Antony and J. Höög for allowing the use of their figure. The author is supported by Award Number R01GM085087 from the National Institute of General Medical Sciences (M.G. is solely responsible for its content).

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  1. Department of Molecular Genetics and Cell Biology, University of Chicago, 920 East 58th Street, Chicago, 60637, Illinois, USA

    Michael Glotzer

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A structural model of the survivin–borealin–INCENP complex

Cytosim (Francois Nedelec's microtubule dynamics simulation program)

Glossary

Cytokinesis

The process by which a single cell divides into two physically distinct daughter cells.

Kinetochore

The proteinaceous structure that serves as a physical link between microtubules and the chromatin during mitosis.

Mitotic spindle

A supramolecular structure comprised of microtubules, chromosomes, motor proteins, MAPs and other components that is responsible for segregating chromosomes during mitosis.

Astral microtubule

A microtubule that emanates radially from the centrosome during metaphase and anaphase.

Abscission

The process that results in the severing of the cytoplasmic bridge, which separates the two daughter cells.

Interpolar microtubule

A microtubule that emanates from one spindle pole and bundles with microtubules that come from the opposite pole.

Midbody

The highly compacted structure at the centre of the cytoplasmic bridge between two nascent daughter cells.

FRAP

(Fluorescence recovery after photobleaching). An imaging technique in which a subset of fluorescent molecules are rendered non-fluorescent by intense illumination. The time course of fluorescence recovery reflects the rate at which molecules exchange.

Centrosome

A structure that is enriched in γ-tubulin that nucleates and organizes microtubule minus ends. The centrosome often contains a pair of centrioles.

Coiled-coil domain

A protein structural domain that mediates subunit oligomerization. Coiled coils contain between two and five helices that twist around each other.

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Glotzer, M. The 3Ms of central spindle assembly: microtubules, motors and MAPs. Nat Rev Mol Cell Biol 10, 9–20 (2009). https://doi.org/10.1038/nrm2609

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