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Cdk1 coordinates cell-surface growth with the cell cycle

Nature Cell Biology volume 9, pages 506–515 (2007)Cite this article

Abstract

The mechanisms that control cell growth during the cell cycle are poorly understood. In budding yeast, cyclin dependent kinase 1 (Cdk1) triggers polarization of the actin cytoskeleton and bud emergence in late G1 through activation of the Cdc42 GTPase. However, Cdk1 is not thought to be required for subsequent growth of the bud. Here, we show that Cdk1 has an unexpected role in controlling bud growth after bud emergence. Moreover, we show that G1 cyclin–Cdk1 complexes specifically phosphorylate multiple proteins associated with Cdc24, the guanine nucleotide-exchange factor (GEF) that activates the Cdc42 GTPase. A mutant form of a Cdc24-associated protein that fails to undergo Cdk1-dependent phosphorylation causes defects in bud growth. These results provide a direct link between Cdk1 activity and the control of polarized cell growth.

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Figure 1: Cdk1 activity is essential for bud growth during the cell cycle.
Figure 2: Cdk1 activity is required for the localization of secretory vesicles, motor proteins and the actin cytoskeleton at sites of polarized growth.
Figure 3: Identification of a Cdc24 exchange factor complex.
Figure 4: Cdk1 activity is required for the initial localization and maintenance of Cdc24 complex components at sites of polarized growth.
Figure 5: Cdc24-complex components are Cln2–Cdk1 substrates in vitro.
Figure 6: Boi1 function requires Cln2–Cdk1 phosphorylation.

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Acknowledgements

We thank J. Krupp at UCSC for his expert technical assistance with electron microscopy and for sectioning samples; C. Zhang and K. Shokat for providing 1NM–PP1; R. Arkowitz for the GFP–Cdc42 strain, tagging plasmids and helpful suggestions, A. Bender for Boi1 antiserum, D. Morgan for the cdk1-as strain and R. Deschaies for the Cln2–HA plasmid; B. Sullivan, A. Royou, S. Harvey and all Kellogg lab members for comments and insightful discussion. This work was supported by a grant from the National Institutes of Health, grant number GM53959.

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Authors and Affiliations

  1. Department of Molecular, Cell and Developmental Biology, University of California, 1156 High Street, Santa Cruz, 95064, CA, USA

    Derek McCusker, Thea A. Egelhofer & Douglas R. Kellogg

  2. Department of Cell Biology, Taplin Biological Mass Spectrometry Facility, Harvard Medical School, 240 Longwood Avenue, Boston, 02115, MA, USA

    Carilee Denison & Steven P. Gygi

  3. Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, CA, USA

    Scott Anderson & John R. Yates 3rd

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Contributions

D.M. and D.K. designed the experiments. Mass spectrometry was carried out by S.A., J.Y., C.D. and S.G. All other experiments were carried out by D.M., with technical assistance from T.E. for a cell-cycle time-course experiment and help from D.K. in CDK activity normalization. D.M. and D.K. analysed the data and wrote the paper.

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Correspondence to Douglas R. Kellogg.

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Supplementary information

Supplementary Information

Supplementary figures S1, S2, S3, S4, S5, S6, Supplementary tables S1 and S2 (PDF 1693 kb)

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McCusker, D., Denison, C., Anderson, S. et al. Cdk1 coordinates cell-surface growth with the cell cycle. Nat Cell Biol 9, 506–515 (2007). https://doi.org/10.1038/ncb1568

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