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.

  • Article
  • Published:

Par-1 regulates stability of the posterior determinant Oskar by phosphorylation

Nature Cell Biology volume 4, pages 337–342 (2002)Cite this article

Abstract

Par-1 kinase is critical for polarization of the Drosophila melanogaster oocyte and the one-cell Caenorhabditis elegans embryo. Although Par-1 localizes specifically to the posterior pole in both cells, neither its targets nor its function at the posterior pole have been elucidated. Here we show that Drosophila Par-1 phosphorylates the posterior determinant Oskar (Osk) and demonstrate genetically that Par-1 is required for accumulation of Osk protein. We show in cell-free extracts that Osk protein is intrinsically unstable and that it is stabilized after phosphorylation by Par-1. Our data indicate that posteriorly localized Par-1 regulates posterior patterning by stabilizing Osk.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: par-1 is required for pole plasm formation.
Figure 2: par-1 is required for accumulation of Osk protein.
Figure 3: par-1 regulates Osk accumulation independently of the osk 3′ UTR.
Figure 4: Par-1 phosphorylates Osk in vitro and in vivo.
Figure 5: Osk is degraded by the ubiquitin-proteasome pathway in Xenopus cell-free extracts.
Figure 6: Phosphorylation by Par-1 stabilizes Osk in extracts of Drosophila ovaries.
Figure 7: A model for the steps that form the positive feedback loop that ensures that Osk accumulates at the posterior pole of the oocyte.

Similar content being viewed by others

References

  1. Guo, S. & Kemphues, K. J. par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed. Cell 81, 611–620 (1995).

    Article  CAS  Google Scholar 

  2. Shulman, J. M., Benton, R. & St Johnston, D. The Drosophila homolog of C. elegans PAR-1 organizes the oocyte cytoskeleton and directs oskar mRNA localization to the posterior pole. Cell 101, 377–388 (2000).

    Article  CAS  Google Scholar 

  3. Tomancak, P. et al. A Drosophila melanogaster homologue of Caenorhabditis elegans par-1 acts at an early step in embryonic-axis formation. Nature Cell Biol. 2, 458–460 (2000).

    Article  CAS  Google Scholar 

  4. Cox, D. N., Lu, B., Sun, T.-S., Williams, L. T. & Jan, Y. N. Drosophila par-1 is required for oocyte differentiation and microtubule organization. Curr. Biol. 11, 75–87 (2001).

    Article  CAS  Google Scholar 

  5. Huynh, J.-R., Shulman, J., Benton, R. & St Johnston, D. Par-1 is required for the maintenance of oocyte fate in Drosophila. Development 128, 1201–1209 (2001).

    CAS  PubMed  Google Scholar 

  6. Drewes, G., Ebneth, A., Preuss, U., Mandelkow, E. M. & Mandelkow, E. MARK, a novel family of protein kinases that phosphorylate microtubule- associated proteins and trigger microtubule disruption. Cell 89, 297–308 (1997).

    Article  CAS  Google Scholar 

  7. Markussen, F. H., Michon, A. M., Breitwieser, W. & Ephrussi, A. Translational control of oskar generates short OSK, the isoform that induces pole plasma assembly. Development 121, 3723–3732 (1995).

    CAS  PubMed  Google Scholar 

  8. Rongo, C., Gavis, E. R. & Lehmann, R. Localization of oskar RNA regulates oskar translation and requires Oskar protein. Development 121, 2737–46 (1995).

    CAS  PubMed  Google Scholar 

  9. Kim-Ha, J., Kerr, K. & Macdonald, P. M. Translational regulation of oskar mRNA by Bruno, an ovarian RNA-binding protein, is essential. Cell 81, 403–412 (1995).

    Article  CAS  Google Scholar 

  10. Webster, P. J., Liang, L., Berg, C. A., Lasko, P. & Macdonald, P. M. Translational repressor Bruno plays multiple roles in development and is widely conserved. Genes Dev 11, 2510–2521 (1997).

    Article  CAS  Google Scholar 

  11. Gunkel, N., Yano, T., Markussen, F. H., Olsen, L. C. & Ephrussi, A. Localization-dependent translation requires a functional interaction between the 5′ and 3′ ends of oskar mRNA. Genes Dev. 12, 1652–1664 (1998).

    Article  CAS  Google Scholar 

  12. Ephrussi, A. & Lehmann, R. Induction of germ cell formation by oskar. Nature 358, 387–392 (1992).

    Article  CAS  Google Scholar 

  13. Smith, J. L., Wilson, J. E. & Macdonald, P. M. Overexpression of oskar directs ectopic activation of nanos and presumptive pole cell formation in Drosophila embryos. Cell 70, 849–859 (1992).

    Article  CAS  Google Scholar 

  14. Ephrussi, A., Dickinson, L. K. & Lehmann, R. Oskar organizes the germ plasm and directs localization of the posterior determinant nanos. Cell 66, 37–50 (1991).

    Article  CAS  Google Scholar 

  15. Kim-Ha, J., Smith, J. L. & Macdonald, P. M. oskar mRNA is localized to the posterior pole of the Drosophila oocyte. Cell 66, 23–35 (1991).

    Article  CAS  Google Scholar 

  16. Hay, B., Jan, L. Y. & Jan, Y. N. Localization of vasa, a component of Drosophila polar granules, in maternal-effect mutants that alter embryonic anteroposterior polarity. Development 109, 425–433 (1990).

    CAS  PubMed  Google Scholar 

  17. Lasko, P. F. & Ashburner, M. Posterior localization of Vasa protein correlates with, but is not sufficient for, pole cell development. Genes Dev. 4, 905–921 (1990).

    Article  CAS  Google Scholar 

  18. Breitwieser, W., Markussen, F. H., Horstmann, H. & Ephrussi, A. Oskar protein interaction with Vasa represents an essential step in polar granule assembly. Genes Dev. 10, 2179–2188 (1996).

    Article  CAS  Google Scholar 

  19. Markussen, F. H., Breitwieser, W. & Ephrussi, A. Efficient translation and phosphorylation of Oskar require Oskar protein and the RNA helicase Vasa. Cold Spring Harb. Symp. Quant. Biol. 62, 13–17 (1997).

    Article  CAS  Google Scholar 

  20. St Johnston, D., Brown, N. H., Gall, J. G. & Jantsch, M. A conserved double-stranded RNA-binding domain. Proc. Natl Acad. Sci. USA 89, 10979–10983 (1992).

    Article  CAS  Google Scholar 

  21. Lasko, P. RNA sorting in Drosophila oocytes and embryos. FASEB J. 13, 421–433 (1999).

    Article  CAS  Google Scholar 

  22. Fuchs, S. Y., Fried, V. A. & Ronai, Z. Stress-activated kinases regulate protein stability. Oncogene 17, 1483–1490 (1998).

    Article  CAS  Google Scholar 

  23. St Johnston, D., Beuchle, D. & Nüsslein-Volhard, C. staufen, a gene required to localize maternal RNAs in the Drosophila egg. Cell 66, 51–63 (1991).

    Article  CAS  Google Scholar 

  24. Kemphues, K. PARsing embryonic polarity. Cell 101, 345–348 (2000).

    Article  CAS  Google Scholar 

  25. Boyd, L., Guo, S., Levitan, D., Stinchcomb, D. T. & Kemphues, K. J. PAR-2 is asymmetrically distributed and promotes association of P granules and PAR-1 with the cortex in C. elegans embryos. Development 122, 3075–3084 (1996).

    CAS  PubMed  Google Scholar 

  26. Bowerman, B., Ingram, M. K. & Hunter, C. P. The maternal par genes and the segregation of cell fate specification activities in early Caenorhabditis elegans embryos. Development 124, 3815–3826 (1997).

    CAS  PubMed  Google Scholar 

  27. Rørth, P. Gal4 in the Drosophila female germline. Mech. Dev. 78, 113–118 (1998).

    Article  Google Scholar 

  28. Murray, A. W. & Kirschner, M. W. Cyclin synthesis drives the early embryonic cell cycle. Nature 339, 275–280 (1989).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank F. Senger, A. Pozniakovsky and R. Lippe for help during purification of recombinant Par-1 protein, A. Jenny for providing Osk protein and antibody, O. Coux for GST-Ubiquitin, N. Gunkel for generation of UAS-par-1 transgenes and T. Vaccari, P. Gönczy and K. Kemphues for comments on the manuscript. We are grateful to P. Tomancak for valuable ideas and discussions. V. R. was supported by EMBO fellowship ALTF 508-1998.

Author information

Authors and Affiliations

  1. European Molecular Biology Laboratory, Meyerhofstraße 1, Postfach 10.2209, Heidelberg, D-69012, Germany

    Veit Riechmann, Gustavo J. Gutierrez, Paolo Filardo, Angel R. Nebreda & Anne Ephrussi

Authors
  1. Veit Riechmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gustavo J. Gutierrez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paolo Filardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Angel R. Nebreda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anne Ephrussi
    View author publications

    You can also search for this author in PubMed Google Scholar

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Riechmann, V., Gutierrez, G., Filardo, P. et al. Par-1 regulates stability of the posterior determinant Oskar by phosphorylation. Nat Cell Biol 4, 337–342 (2002). https://doi.org/10.1038/ncb782

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb782

This article is cited by

Search

Advanced 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