Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Extracellular control of cell size

An Erratum to this article was published on 01 May 2002

A Correction to this article was published on 01 November 2001

An Erratum to this article was published on 01 November 2001

Abstract

Both cell growth (cell mass increase) and progression through the cell division cycle are required for sustained cell proliferation1. Proliferating cells in culture tend to double in mass before each division2, but it is not known how growth and division rates are co-ordinated to ensure that cell size is maintained1,3,4,5. The prevailing view is that coordination is achieved because cell growth is rate-limiting for cell-cycle progression6,7,8,9,10. Here, we challenge this view. We have investigated the relationship between cell growth and cell-cycle progression in purified rat Schwann cells, using two extracellular signal proteins that are known to influence these cells11,12,13. We find that glial growth factor (GGF) can stimulate cell-cycle progression without promoting cell growth. We have used this restricted action of GGF to show that, for cultured Schwann cells, cell growth rate alone does not determine the rate of cell-cycle progression and that cell size at division is variable and depends on the concentrations of extracellular signal proteins that stimulate cell-cycle progression, cell growth, or both.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Aphidicolin-arrested Schwann cells continue to grow in complete medium and become larger than untreated proliferating cells.
Figure 2: GGF promotes cell-cycle progression, and IGF-I promotes both cell growth and cell-cycle progression.
Figure 3: A higher concentration of GGF shortens the cell-cycle time and decreases cell size.
Figure 4

Similar content being viewed by others

References

  1. Su, T. T. & O'Farrell, P. H. Curr. Biol. 8, R687–R689 (1998).

    Article  CAS  Google Scholar 

  2. Mitchison, J. M. The Biology of the Cell Cycle (Cambridge Univ. Press, London, 1971).

    Google Scholar 

  3. Coelho, C. M. & Leevers, S. J. J. Cell Sci. 113, 2927–2934 (2000).

    CAS  PubMed  Google Scholar 

  4. Conlon, I. & Raff, M. Cell 96, 235–244 (1999).

    Article  CAS  Google Scholar 

  5. Stocker, H. & Hafen, E. Curr. Opin. Genet. Dev. 10, 529–535 (2000).

    Article  CAS  Google Scholar 

  6. Fantes, P. A. J. Cell Sci. 24, 51–67 (1977).

    CAS  PubMed  Google Scholar 

  7. Johnston, G. C., Pringle, J. R. & Hartwell, L. H. Exp. Cell Res. 105, 79–98 (1977).

    Article  CAS  Google Scholar 

  8. Nurse, P. Phil. Trans. R. Soc. Lond. B 332, 271–276 (1991).

    Article  CAS  Google Scholar 

  9. Polymenis, M. & Schmidt, E. V. Curr. Opin. Genet. Dev. 9, 76–80 (1999).

    Article  CAS  Google Scholar 

  10. Prescot, D. H. Exp. Cell Res. 11, 86–98 (1956).

    Article  Google Scholar 

  11. Burden, S. & Yarden, Y. Neuron 18, 847–855 (1997).

    Article  CAS  Google Scholar 

  12. Cheng, L., Esch, F. S., Marchionni, M. A. & Mudge, A. W. Mol. Cell. Neurosci. 12, 141–156 (1998).

    Article  CAS  Google Scholar 

  13. Stewart, H. J. et al. Eur. J. Neurosci. 8, 553–564 (1996).

    Article  CAS  Google Scholar 

  14. Ikegami, S. et al. Nature 275, 458–460 (1978).

    Article  CAS  Google Scholar 

  15. Dunn, G. A. & Zicha, D. Symp. Soc. Exp. Biol. 47, 91–106 (1993).

    CAS  PubMed  Google Scholar 

  16. Polymenis, M. & Schmidt, E. V. Genes. Dev. 11, 2522–2531 (1997).

    Article  CAS  Google Scholar 

  17. Johnston, L. A., Prober, D. A., Edgar, B. A., Eisenman, R. N. & Gallant, P. Cell 98, 779–790 (1999).

    Article  CAS  Google Scholar 

  18. Prober, D. A. & Edgar, B. A. Cell 100, 435–446 (2000).

    Article  CAS  Google Scholar 

  19. Weinkove, D., Neufeld, T. P., Twardzik, T., Waterfield, M. D. & Leevers, S. J. Curr. Biol. 9, 1019–1029 (1999).

    Article  CAS  Google Scholar 

  20. Edgar, B. A. Nature Cell Biol. 1, E191–E193 (1999).

    Article  CAS  Google Scholar 

  21. Neufeld, T. P., de la Cruz, A. F., Johnston, L. A. & Edgar, B. A. Cell 93, 1183–1193 (1998).

    Article  CAS  Google Scholar 

  22. Cheng, L., Khan, M. & Mudge, A. W. J. Cell Biol. 129, 789–796 (1995).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank M. Marchionni for the recombinant GGF 2, L. Cheng for her expert help, A. Lloyd, S. Leevers, D. Knight, P. Nurse, R. Brooks and the Raff and Lloyd labs for helpful discussions, and the Medical Research Council for support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ian J. Conlon.

Supplementary information

Supplementary figures

Figure S1 IGF-I but not GGF promotes the growth of quiescent cells in the presence of aphidicolin. (PDF 33 kb)

Figure S2 Cells in IGF-I (100 ng ml -1 ), forskolin and aphidicolin grow at the same rate in high (20 ng ml -1 ) or low (2 ng ml -1 ) GGF.

Figure S3 Cells proliferating in IGF-I, GGF and forskolin become progressively smaller

Rights and permissions

Reprints and permissions

About this article

Cite this article

Conlon, I., Dunn, G., Mudge, A. et al. Extracellular control of cell size. Nat Cell Biol 3, 918–921 (2001). https://doi.org/10.1038/ncb1001-918

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb1001-918

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing