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Centrosomal MPF triggers the mitotic and morphogenetic switches of fission yeast

Nature Cell Biology volume 15, pages 88–95 (2013)Cite this article

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Abstract

Activation of mitosis-promoting factor (MPF) drives mitotic commitment1. In human cells active MPF appears first on centrosomes2. We show that local activation of MPF on the equivalent organelle of fission yeast, the spindle pole body (SPB), promotes Polo kinase activity at the SPBs long before global MPF activation drives mitotic commitment. Artificially promoting MPF or Polo activity at various locations revealed that this local control of Plo1 activity on G2 phase SPBs dictates the timing of mitotic commitment. Cytokinesis of the rod-shaped fission yeast cell generates a naive, new, cell end. Growth is restricted to the experienced old end until a point in G2 phase called new end take off (NETO) when bipolar growth is triggered3. NETO coincided with MPF activation of Plo1 on G2 phase SPBs (ref. 4). Both MPF and Polo activities were required for NETO and both induced NETO when ectopically activated at interphase SPBs. NETO promotion by MPF required polo. Thus, local MPF activation on G2 SPBs directs polo kinase to control at least two distinct and temporally separated, cell-cycle transitions at remote locations.

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Figure 1: MPF activity controls Plo1.GFP recruitment to the SPB in late G2 phase.
Figure 2: Ectopic activation of either Plo1 or MPF on G2 SPBs promotes mitotic commitment.
Figure 3: NETO is triggered by Plo1 activation/recruitment on the G2 SPB.
Figure 4: MPF activation on the SPB triggers NETO in a Plo1-dependent manner.
Figure 5: Model of feedback loop activation on the SPB and its subsequent propagation throughout the cell to promote mitotic commitment.

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Acknowledgements

We thank B. Hodgson for technical assistance; V. Doye (Insitut Jacques Monod, Paris, France), D. Mulvihill (University of Kent, UK), U. Fleig (Düsseldorf, Germany) and D. Feret (Paterson Institute, UK) for strains; K. Gull (Oxford University, UK) and H. Ohkura (Edinburgh University, UK) for antibodies; D. Feret (Paterson Institute, UK), G. Pereira (DKFZ, Germany) and A. Carr (GDSC, Sussex, UK) for plasmids; and D. Bitton (Paterson Institute, UK) for discussions during the design of plo1.as8. This work was supported by Cancer Research UK (CRUK) grant number C147/A6058. V.S. and A.K. were supported by the Swiss National Science Foundation and EPFL.

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Author notes

  1. Victor A. Tallada

    Present address: Present address: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide/Consejo Superior de Investigaciones Cientificas, 41013 Sevilla, Spain,

  2. Agnes Grallert and Avinash Patel: These authors contributed equally to this work

Authors and Affiliations

  1. CRUK Cell Division Group, Paterson Institute for Cancer Research, Wilmslow Road, Manchester, M20 4BX, UK

    Agnes Grallert, Avinash Patel, Victor A. Tallada, Kuan Yoow Chan & Iain M. Hagan

  2. Advanced Imaging and Flow Cytometry, Paterson Institute for Cancer Research, Wilmslow Road, Manchester, M20 4BX, UK

    Steven Bagley

  3. EPFL SV ISREC UPSIM, SV2.1830, Station 19, CH-1015 Lausanne, Switzerland

    Andrea Krapp & Viesturs Simanis

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Contributions

I.M.H. conceived the study. A.K. and V.S. generated cdc2.as. A.P. generated the conditional polo kinase alleles, including Plo1.RL. V.A.T. and K.Y.C. carried out the imaging work in Fig. 1. A.G. performed the remainder of the experiments with occasional assistance from A.P. and K.Y.C. for more complex experiments and cloning. I.M.H. wrote the manuscript with input and discussions from all authors.

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Correspondence to Iain M. Hagan.

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The authors declare no competing financial interests.

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Grallert, A., Patel, A., Tallada, V. et al. Centrosomal MPF triggers the mitotic and morphogenetic switches of fission yeast. Nat Cell Biol 15, 88–95 (2013). https://doi.org/10.1038/ncb2633

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