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Microtubule nucleation: beyond the template

Nature Reviews Molecular Cell Biology volume 18, pages 702–710 (2017)Cite this article

Subjects

Key Points

  • Assembly of the microtubule nucleus is an energetically unfavourable process.

  • Microtubule nucleation is stimulated and can be controlled by the following two principal activities: by providing a stable template (such as the γ-tubulin ring complex (γTuRC) or a severed microtubule) or by the action of microtubule-associated proteins (MAPs) that stabilize the nascent microtubule 'nucleus'.

  • MAPs with the potential to promote microtubule nucleation include the microtubule polymerases of the XMAP215 family and suppressors of microtubule dynamics.

  • These stabilizing MAPs are also likely to provide an additional layer of control over microtubule nucleation by counteracting microtubule destabilizers that have been shown to inhibit nucleation.

  • The different activities most likely act synergistically in the cell environment to facilitate efficient microtubule nucleation.

Abstract

Microtubules are cytoskeletal filaments central to a wide range of essential cellular functions in eukaryotic cells. Consequently, cells need to exert tight control over when, where and how many microtubules are being made. Whereas the regulation of microtubule dynamics is well studied, the molecular mechanisms of microtubule nucleation are still poorly understood. Next to the established master template of nucleation, the γ-tubulin ring complex, other microtubule-associated proteins that affect microtubule dynamic properties have recently been found to contribute to nucleation. It has begun to emerge that the nucleation efficiency is controlled not only by template activity but also by, either additionally or alternatively, the stabilization of the nascent microtubule 'nucleus'. This suggests a simple conceptual framework for the mechanisms regulating microtubule nucleation in cells.

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Figure 1: Hypothetical pathway of spontaneous filament nucleation.
Figure 2: Visualization of microtubule nuclei.
Figure 3: Enhancing microtubule nucleation.
Figure 4: Different microtubule nucleation templates.

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Acknowledgements

This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001163), the UK Medical Research Council (FC001163), and the Wellcome Trust (FC001163). J.R acknowledges funding from a Sir Henry Wellcome Postdoctoral Fellowship (100145/Z/12/Z), and T.S., from the European Research Council (Advanced Grant, project 323042).

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  1. The Francis Crick Institute, 1 Midland Road, NW1 1AT, London, UK

    Johanna Roostalu & Thomas Surrey

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  1. Johanna Roostalu
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  2. Thomas Surrey
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Contributions

Both T.S. and J.R. discussed the content of the manuscript and contributed substantially to the writing and review/editing of the manuscript before its submission. J.R. assembled the figures.

Corresponding authors

Correspondence to Johanna Roostalu or Thomas Surrey.

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PowerPoint slides

Glossary

Plus end

Fast growing end of the polar microtubule filament, with exposed β-tubulin at its terminus (Box 1).

Minus end

Slowly growing end of the polar microtubule filament, with exposed α-tubulin at its terminus (Box 1).

Cortical microtubules

Ordered acentrosomal array of microtubules at the plant cell cortex that is important for cell morphogenesis.

Stathmin/Op18

Small, 18 kDa, disordered protein that acts as a tubulin-sequestering factor by binding simultaneously to two tubulin dimers, thereby lowering the polymerization-competent tubulin concentration in the living cell.

Centrosomes

Non-membranous organelles that act as the main microtubule organizing and nucleating centres in somatic animal cells.

Axonemes

Microtubule-based core structural components of cilia consisting of either 9 microtubules organized in a circle (primary cilia) or 9 microtubule doublets organized in a circle with an additional microtubule pair in the middle (motile cilia).

TOG domains

Paddle-shaped tubulin-binding domains composed of six HEAT repeat motifs found in XMAP215, CLASP and crescerin family proteins.

Kinetochore

Large multi-protein complex usually assembled on centromeric DNA that serves as a site of interaction between chromosomes and microtubules.

Aurora A kinase

Serine/threonine kinase with numerous functions in mitosis and meiosis, including centrosome maturation and spindle assembly.

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Roostalu, J., Surrey, T. Microtubule nucleation: beyond the template. Nat Rev Mol Cell Biol 18, 702–710 (2017). https://doi.org/10.1038/nrm.2017.75

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