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.

  • Letter
  • Published:

Egalitarian binds dynein light chain to establish oocyte polarity and maintain oocyte fate

Abstract

In many cell types polarized transport directs the movement of mRNAs and proteins from their site of synthesis to their site of action, thus conferring cell polarity1. The cytoplasmic dynein microtubule motor complex is involved in this process. In Drosophila melanogaster, the Egalitarian (Egl) and Bicaudal-D (BicD) proteins are also essential for the transport of macromolecules to the oocyte and to the apical surface of the blastoderm embryo2,3,4,5. Hence, Egl and BicD, which have been shown to associate4, may be part of a conserved core localization machinery in Drosophila, although a direct association between these molecules and the dynein motor complex has not been shown. Here we report that Egl interacts directly with Drosophila dynein light chain (Dlc), a microtubule motor component, through an Egl domain distinct from that which binds BicD4. We propose that the Egl–BicD complex is loaded through Dlc onto the dynein motor complex thereby facilitating transport of cargo. Consistent with this model, point mutations that specifically disrupt Egl–Dlc association also disrupt microtubule-dependant trafficking both to and within the oocyte, resulting in a loss of oocyte fate maintenance and polarity. Our data provide a direct link between a molecule necessary for oocyte specification and the microtubule motor complex, and supports the hypothesis that microtubule-mediated transport is important for preserving oocyte fate.

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: Egl associates directly with Dlc.
Figure 2: Oocyte fate maintenance is impaired in egl3e mutant ovaries.
Figure 3: egldlc2pt mutant ovaries show a phenotype similar to egl3e mutant ovaries.
Figure 4: dlc mutant germ-line clones do not maintain oocyte fate.

Similar content being viewed by others

References

  1. Tekotte, H. & Davis, I. Intracellular mRNA localization: motors move messages. Trends Genet. 18, 636–642 (2002).

    Article  CAS  Google Scholar 

  2. Suter, B., Romberg, L.M. & Steward, R. Bicaudal-D, a Drosophila gene involved in developmental asymmetry: localized transcript accumulation in ovaries and sequence similarity to myosin heavy chain tail domains. Genes Dev. 3, 1957–1968 (1989).

    Article  CAS  Google Scholar 

  3. Wharton, R.P. & Struhl, G. Structure of the Drosophila BicaudalD protein and its role in localizing the posterior determinant nanos. Cell 59, 881–892 (1989).

    Article  CAS  Google Scholar 

  4. Mach, J.M. & Lehmann, R. An Egalitarian–BicaudalD complex is essential for oocyte specification and axis determination in Drosophila. Genes Dev. 11, 423–435 (1997).

    Article  CAS  Google Scholar 

  5. Bullock, S.L. & Ish-Horowicz, D. Conserved signals and machinery for RNA transport in Drosophila oogenesis and embryogenesis. Nature 414, 611–616 (2001).

    Article  CAS  Google Scholar 

  6. Moser, M.J., Holley, W.R., Chatterjee, A. & Mian, I.S. The proofreading domain of Escherichia coli DNA polymerase I and other DNA and/or RNA exonuclease domains. Nucleic Acids Res. 25, 5110–5118 (1997).

    Article  CAS  Google Scholar 

  7. Bernad, A., Blanco, L., Lazaro, J.M., Martin, G. & Salas, M. A conserved 3′–5′ exonuclease active site in prokaryotic and eukaryotic DNA polymerases. Cell 59, 219–228 (1989).

    Article  CAS  Google Scholar 

  8. Rodriguez-Crespo, I. et al. Identification of novel cellular proteins that bind to the LC8 dynein light chain using a pepscan technique. FEBS Lett. 503, 135–141 (2001).

    Article  CAS  Google Scholar 

  9. Puthalakath, H., Huang, D.C., O'Reilly, L.A., King, S.M. & Strasser, A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol. Cell 3, 287–296 (1999).

    Article  CAS  Google Scholar 

  10. Day, C.L. et al. Localisation of dynein light chains 1 and 2 and their pro-apoptotic ligands. Biochem. J. 377, 597–605 (2004).

    Article  CAS  Google Scholar 

  11. Carpenter, A.T. Egalitarian and the choice of cell fates in Drosophila melanogaster oogenesis. Ciba Found. Symp. 182, 223–254 (1994).

    CAS  PubMed  Google Scholar 

  12. Huynh, J.R. & St Johnston, D. The role of BicD, Egl, Orb and the microtubules in the restriction of meiosis to the Drosophila oocyte. Development 127, 2785–2794 (2000).

    CAS  PubMed  Google Scholar 

  13. Li, M., McGrail, M., Serr, M. & Hays, T.S. Drosophila cytoplasmic dynein, a microtubule motor that is asymmetrically localized in the oocyte. J. Cell Biol. 126, 1475–1494 (1994).

    Article  CAS  Google Scholar 

  14. Dick, T., Ray, K., Salz, H.K. & Chia, W. Cytoplasmic dynein (ddlc1) mutations cause morphogenetic defects and apoptotic cell death in Drosophila melanogaster. Mol. Cell Biol. 16, 1966–1977 (1996).

    Article  CAS  Google Scholar 

  15. Mohler, J. & Wieschaus, E.F. Dominant maternal-effect mutations of Drosophila melanogaster causing the production of double-abdomen embryos. Genetics 112, 803–822 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Lehmann, R. & Nusslein-Volhard, C. The maternal gene nanos has a central role in posterior pattern formation of the Drosophila embryo. Development 112, 679–691 (1991).

    CAS  PubMed  Google Scholar 

  17. van Eeden, F.J., Palacios, I.M., Petronczki, M., Weston, M.J. & St Johnston, D. Barentsz is essential for the posterior localization of oskar mRNA and colocalizes with it to the posterior pole. J. Cell Biol. 154, 511–523 (2001).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  19. Swan, A. & Suter, B. Role of Bicaudal-D in patterning the Drosophila egg chamber in mid-oogenesis. Development 122, 3577–3586 (1996).

    CAS  PubMed  Google Scholar 

  20. Bolivar, J. et al. Centrosome migration into the Drosophila oocyte is independent of BicD and Egl, and of the organisation of the microtubule cytoskeleton. Development 128, 1889–1897 (2001).

    CAS  PubMed  Google Scholar 

  21. Hoogenraad, C.C. et al. Bicaudal D induces selective dynein-mediated microtubule minus end-directed transport. Embo J. 22, 6004–6015 (2003).

    Article  CAS  Google Scholar 

  22. Hoogenraad, C.C. et al. Mammalian Golgi-associated Bicaudal-D2 functions in the dynein–dynactin pathway by interacting with these complexes. Embo J. 20, 4041–4054 (2001).

    Article  CAS  Google Scholar 

  23. Pelegri, F.P. Chromatin Regulators and the Determination of Embryonic Polarity in Drosophila. Thesis, 285–292, Massachusetts Institute of Technology, 1994.

    Google Scholar 

  24. Schupbach, T. & Wieschaus, E. Female sterile mutations on the second chromosome of Drosophila melanogaster. I. Maternal effect mutations. Genetics 121, 101–117 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Lindsley, D.L. & Zimm, G.G. The genome of Drosophila melanogaster. 851 (Academic Press, San Diego, 1992).

    Google Scholar 

  26. Vidal, M., Brachmann, R.K., Fattaey, A., Harlow, E. & Boeke, J.D. Reverse two-hybrid and one-hybrid systems to detect dissociation of protein-protein and DNA-protein interactions. Proc. Natl Acad. Sci. USA 93, 10315–10320 (1996).

    Article  CAS  Google Scholar 

  27. Huang, D.C., Cory, S. & Strasser, A. Bcl-2, Bcl-xL and adenovirus protein E1B19kD are functionally equivalent in their ability to inhibit cell death. Oncogene 14, 405–414 (1997).

    Article  CAS  Google Scholar 

  28. Grussenmeyer, T., Scheidtmann, K.H., Hutchinson, M.A., Eckhart, W. & Walter, G. Complexes of polyoma virus medium T antigen and cellular proteins. Proc. Natl Acad. Sci. USA 82, 7952–7954 (1985).

    Article  CAS  Google Scholar 

  29. Xu, T. & Rubin, G.M. Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 117, 1223–1237 (1993).

    CAS  PubMed  Google Scholar 

  30. 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 

  31. Navarro, C., Lehmann, R. & Morris, J. Oogenesis: Setting one sister above the rest. Curr. Biol. 11, R162–R165 (2001).

    Article  CAS  Google Scholar 

  32. Theurkauf, W.E., Alberts, B.M., Jan, Y.N. & Jongens, T.A. A central role for microtubules in the differentiation of Drosophila oocytes. Development 118, 1169–1180 (1993).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We wish to thank the members of the Lehmann Lab past and present for advice and reading of the manuscript. We thank K. Albrecht, J. Morris, L. Gilboa, V. Barbosa, D. Ish-Horowicz, S. Bullock and I. Davis for discussions. We thank F. Pelegri and A. Ephrussi for originally isolating the egl3e allele and C. Chang for technical assistance. We also thank M. Grunwald for making the Egl-Myc transgenic line. C.N. was partially supported by the Ann L. Siegel fellowship of the American Cancer Society and the Howard Hughes Medical Institute. H.P., J.A. and A.S. are supported in part by a National Health and Medical Research Council Program grant. R.L. is an investigator of the Howard Hughes Medical Institute.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ruth Lehmann.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary figures

Supplementary Information, Fig. S1 (PDF 987 kb)

Supplementary Information, Fig. S2

Supplementary Information, Table 1 (DOC 20 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Navarro, C., Puthalakath, H., Adams, J. et al. Egalitarian binds dynein light chain to establish oocyte polarity and maintain oocyte fate. Nat Cell Biol 6, 427–435 (2004). https://doi.org/10.1038/ncb1122

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb1122

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