Extracellular control of cell size (original) (raw)

Nature Cell Biology volume 3, pages 918–921 (2001)Cite this article

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

Subscribe to this journal

Receive 12 print issues and online access

$209.00 per year

only $17.42 per issue

Buy this article

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

Additional access options:

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

  1. MRC Laboratory for Molecular Cell Biology and the Biology Department, University College London, London, WC1E 6BT, UK
    Ian J. Conlon, Anne W. Mudge & Martin C. Raff
  2. MRC Muscle and Cell Motility Unit, The Randall Centre, New Hunt's House, Guy's Campus, London, SE1 1UL, UK
    Graham A. Dunn

Authors

  1. Ian J. Conlon
    You can also search for this author inPubMed Google Scholar
  2. Graham A. Dunn
    You can also search for this author inPubMed Google Scholar
  3. Anne W. Mudge
    You can also search for this author inPubMed Google Scholar
  4. Martin C. Raff
    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toIan 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

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

This article is cited by