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Centrosome function and assembly in animal cells

Nature Reviews Molecular Cell Biology volume 16, pages 611–624 (2015)Cite this article

Subjects

Key Points

  • Centrosomes are not essential for cell division in most animal cells, although they contribute to the efficiency of mitotic spindle assembly.

  • Centrosome loss is tolerated surprisingly well in fly cells, but it normally induces a p53-dependent block to proliferation or apoptosis in vertebrate cells.

  • Centrosome dysfunction in humans may promote cancer by increasing levels of chromosomal instability and/or the metastatic potential of cancer cells, although strong genetic evidence for this link is lacking.

  • Strong genetic evidence links centrosome dysfunction to microcephaly and primordial dwarfism in humans, although the reasons for this link are unclear.

  • There have been dramatic recent advances in our molecular understanding of how centrioles and centrosomes assemble.

  • In flies and in worms, the SPD2 and Polo or Polo-like kinase 1 (PLK1) proteins cooperate with Cnn (in flies) or SPD-5 (in worms), to drive the assembly of a scaffold structure around the mother centriole during mitosis that functions to recruit other proteins to the mitotic centrosome.

Abstract

It has become clear that the role of centrosomes extends well beyond that of important microtubule organizers. There is increasing evidence that they also function as coordination centres in eukaryotic cells, at which specific cytoplasmic proteins interact at high concentrations and important cell decisions are made. Accordingly, hundreds of proteins are concentrated at centrosomes, including cell cycle regulators, checkpoint proteins and signalling molecules. Nevertheless, several observations have raised the question of whether centrosomes are essential for many cell processes. Recent findings have shed light on the functions of centrosomes in animal cells and on the molecular mechanisms of centrosome assembly, in particular during mitosis. These advances should ultimately allow the in vitro reconstitution of functional centrosomes from their component proteins to unlock the secrets of these enigmatic organelles.

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Figure 1: Centriole, centrosome and cilium behaviour during the cell cycle.
Figure 2: Consequences of a lack of centrosomes on cell division and proliferation in flies and in mice.
Figure 3: A model of the molecular pathways of centriole and mitotic centrosome assembly in worms, flies and humans.
Figure 4: A model of mitotic pericentriolar material (PCM) assembly in flies.

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Acknowledgements

The authors thank Hisham Bazzi and Kathryn Anderson for the mouse embryo images shown in Figure 2, and several colleagues who communicated unpublished data and provided helpful discussion. The work in the author's labs is funded by a Wellcome Trust Senior Investigator Award (104575) (AW and JWR), a Wellcome Trust Strategic Award to Micron Oxford (091911) (AW) and a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and The Royal Society (105653) (PTC).

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  1. Department of Zoology, University of Cambridge, Downing Street, Cambridge, CB2 3EJ, UK

    Paul T. Conduit

  2. The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK

    Alan Wainman & Jordan W. Raff

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Conduit, P., Wainman, A. & Raff, J. Centrosome function and assembly in animal cells. Nat Rev Mol Cell Biol 16, 611–624 (2015). https://doi.org/10.1038/nrm4062

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