Letter | Published:

Control of daughter centriole formation by the pericentriolar material

Nature Cell Biology volume 10, pages 322328 (2008) | Download Citation

Subjects

Abstract

Controlling the number of its centrioles is vital for the cell, as supernumerary centrioles cause multipolar mitosis and genomic instability1,2. Normally, one daughter centriole forms on each mature (mother) centriole3,4; however, a mother centriole can produce multiple daughters within a single cell cycle5,6. The mechanisms that prevent centriole 'overduplication' are poorly understood. Here we use laser microsurgery to test the hypothesis that attachment of the daughter centriole to the wall of the mother inhibits formation of additional daughters7,8. We show that physical removal of the daughter induces reduplication of the mother in S-phase-arrested cells. Under conditions when multiple daughters form simultaneously on a single mother, all of these daughters must be removed to induce reduplication. The number of daughter centrioles that form during reduplication does not always match the number of ablated daughter centrioles. We also find that exaggeration of the pericentriolar material (PCM) by overexpression of the PCM protein pericentrin9 in S-phase-arrested CHO cells induces formation of numerous daughter centrioles. We propose that that the size of the PCM cloud associated with the mother centriole restricts the number of daughters that can form simultaneously.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Centrosome aberrations: cause or consequence of cancer progression? Nature Rev. Cancer 2, 815–825 (2002).

  2. 2.

    & The good, the bad and the ugly: the practical consequences of centrosome amplification. Curr. Opin. Cell Biol. 16, 49–54 (2004).

  3. 3.

    & Controlling centrosome number: licenses and blocks. Curr. Opin. Cell Biol. 18, 74–78 (2006).

  4. 4.

    et al. Centriole overduplication through the concurrent formation of multiple daughter centrioles at single maternal templates. Oncogene 26, 6280–6288 (2007).

  5. 5.

    et al. Dissociation of centrosome replication events from cycles of DNA synthesis and mitotic division in hydroxyurea-arrested Chinese hamster ovary cells. J. Cell Biol. 130, 105–115 (1995).

  6. 6.

    et al. Plk4-induced centriole biogenesis in human cells. Dev. Cell 13, 190–202 (2007).

  7. 7.

    & Centrosome number is controlled by a centrosome-intrinsic block to reduplication. Nature Cell Biol. 5, 539–544 (2003).

  8. 8.

    & Mechanism limiting centrosome duplication to once per cell cycle. Nature 442, 947–951 (2006).

  9. 9.

    et al. Pericentrin and γ-tubulin form a protein complex and are organized into a novel lattice at the centrosome. J. Cell Biol. 141, 163–174 (1998).

  10. 10.

    et al. Centriole disassembly in vivo and its effect on centrosome structure and function in vertebrate cells. J. Cell Biol. 143, 1575–1589 (1998).

  11. 11.

    & Centriole cycle in Chinese hamster ovary cells as determined by whole-mount electron microscopy. J. Cell Biol. 91, 814–821 (1981).

  12. 12.

    & Centrioles in the cell cycle. I. Epithelial cells. J. Cell Biol. 93, 938–949 (1982).

  13. 13.

    , , & Centrosome organization and centriole architecture: their sensitivity to divalent cations. J. Struct. Biol. 108, 107–128 (1992).

  14. 14.

    What is the function of centrioles? J. Cell. Biochem. 100, 916–922 (2007).

  15. 15.

    , & Anomalous centriole configurations are detected in Drosophila wing disc cells upon Cdk1 inactivation. J. Cell Sci. 116, 137–143 (2003).

  16. 16.

    , , & The Polo kinase Plk4 functions in centriole duplication. Nature Cell Biol. 7, 1140–1146 (2005).

  17. 17.

    , , , & The respective contributions of the mother and daughter centrioles to centrosome activity and behavior in vertebrate cells. J. Cell Biol. 149, 317–330 (2000).

  18. 18.

    et al. De novo formation of centrosomes in vertebrate cells arrested during S phase. J. Cell Biol. 158, 1171–1181 (2002).

  19. 19.

    et al. The de novo centriole assembly pathway in HeLa cells: cell cycle progression and centriole assembly/maturation. J. Cell Biol. 168, 713–720 (2005).

  20. 20.

    et al. Cell cycle progression and de novo centriole assembly after centrosomal removal in untransformed human cells. J. Cell Biol. 176, 173–182 (2007).

  21. 21.

    et al. De novo formation of basal bodies in Naegleria gruberi: regulation by phosphorylation. J. Cell Biol. 169, 719–724 (2005).

  22. 22.

    et al. Centriole assembly requires both centriolar and pericentriolar material proteins. Dev. Cell 7, 815–829 (2004).

  23. 23.

    , , , & Centriole assembly in Caenorhabditis elegans. Nature 444, 619–623 (2006).

  24. 24.

    , , , & Revisiting the role of the mother centriole in centriole biogenesis. Science 316, 1046–1050 (2007).

  25. 25.

    , , & Overexpressing centriole-replication proteins in vivo induces centriole overduplication and de novo formation. Curr. Biol. 17, 834–843 (2007).

  26. 26.

    , & Kinetics and regulations of de novo centriole assembly: implications for the mechanism of centriole duplication. Curr. Biol. 11, 308–317 (2001).

  27. 27.

    , , , & Cytoplasmic dynein-mediated assembly of pericentrin and γ-tubulin onto centrosomes. Mol. Biol. Cell 11, 2047–2056 (2000).

  28. 28.

    , , , & in Laser Manipulations of Cells and Tissues (eds. Berns, M. W. & Greulich, K. O.) 237–266 (Elsevier, 2007).

  29. 29.

    , , & Direct interaction of pericentrin with cytoplasmic dynein light intermediate chain contributes to mitotic spindle organization. J. Cell Biol. 147, 481–492 (1999).

  30. 30.

    et al. Regulated HsSAS-6 levels ensure formation of a single procentriole per centriole during the centrosome duplication cycle. Dev. Cell 13, 203–213 (2007).

Download references

Acknowledgements

We thank the members of our lab for fruitful discussions. Special thanks to Brian M. Davis and Igor B. Roninson for their help with construction of the centrin–GFP lentivirus and Yimin Dong for assistance with 3D reconstructions. We also thank Kip Sluder, Conly Rieder and Michael Koonce for critical comments on the manuscript. This work was supported by grants from the National Institutes of Health (GM GM59363) and the Human Frontiers Science Program (RGP0064). Construction of our laser microsurgery workstation was supported in part by a fellowship from Nikon/Marine Biological Laboratory (A. K.). We acknowledge use of the Wadsworth Center's Electron Microscopy Core Facility.

Author information

Affiliations

  1. Division of Molecular Medicine, Wadsworth Center, Albany, New York State Department of Health, Albany, New York 12201-0509, USA.

    • Jadranka Loncarek
    • , Polla Hergert
    • , Valentin Magidson
    •  & Alexey Khodjakov
  2. Marine Biological Laboratory, Woods Hole, Massachusetts 02543, USA.

    • Alexey Khodjakov

Authors

  1. Search for Jadranka Loncarek in:

  2. Search for Polla Hergert in:

  3. Search for Valentin Magidson in:

  4. Search for Alexey Khodjakov in:

Contributions

Experiments were conducted by J. L.; P. H. was responsible for EM preparation and data collection; V. M. designed, assembled and maintained the laser microsurgery workstation; A. K. directed the work. Experiments were planned by J. L. and A. K.

Corresponding author

Correspondence to Alexey Khodjakov.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    Supplementary figures S1, S2, S3, S4, S5, S6, S7, S8, Movie legends and Supplementary text

Videos

  1. 1.

    Supplementary Information

    Supplementary Movie 1

  2. 2.

    Supplementary Information

    Supplementary Movie 2

  3. 3.

    Supplementary Information

    Supplementary Movie 3

  4. 4.

    Supplementary Information

    Supplementary Movie 4

  5. 5.

    Supplementary Information

    Supplementary Movie 5

  6. 6.

    Supplementary Information

    Supplementary Movie 6

  7. 7.

    Supplementary Information

    Supplementary Movie 7

  8. 8.

    Supplementary Information

    Supplementary Movie 8

  9. 9.

    Supplementary Information

    Supplementary Movie 9

  10. 10.

    Supplementary Information

    Supplementary Movie 10

  11. 11.

    Supplementary Information

    Supplementary Movie 11

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/ncb1694

Further reading