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:

Bicaudal-D regulates COPI-independent Golgi–ER transport by recruiting the dynein–dynactin motor complex

Nature Cell Biology volume 4, pages 986–992 (2002)Cite this article

An Erratum to this article was published on 01 January 2003

Abstract

The small GTPase Rab6a is involved in the regulation of membrane traffic from the Golgi apparatus towards the endoplasmic reticulum (ER) in a coat complex coatomer protein I (COPI)-independent pathway1,2,3,4,5,6. Here, we used a yeast two-hybrid approach to identify binding partners of Rab6a. In particular, we identified the dynein–dynactin-binding protein Bicaudal-D1 (BICD1), one of the two mammalian homologues of Drosophila Bicaudal-D7,8,9,10. BICD1 and BICD2 colocalize with Rab6a on the trans-Golgi network (TGN) and on cytoplasmic vesicles, and associate with Golgi membranes in a Rab6-dependent manner. Overexpression of BICD1 enhances the recruitment of dynein–dynactin to Rab6a-containing vesicles. Conversely, overexpression of the carboxy-terminal domain of BICD, which can interact with Rab6a but not with cytoplasmic dynein, inhibits microtubule minus-end-directed movement of green fluorescent protein (GFP)–Rab6a vesicles and induces an accumulation of Rab6a and COPI-independent ER cargo in peripheral structures. These data suggest that coordinated action between Rab6a, BICD and the dynein–dynactin complex controls COPI-independent Golgi–ER transport.

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: Direct binding of BICD and Rab6, and colocalization of BICD, Rab6 and STB.
Figure 2: Rab6a mutants and depletion of Rab6 affect the localization of BICD1.
Figure 3: The effect of BICD1 overexpression on the localization of dynein–dynactin.
Figure 4: Overexpression of BICD1 and incubation at 20 °C results in extensive tubulation.
Figure 5: Peripheral accumulation of Rab6a vesicles and ER cargo.

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Rothman, J. E. & Wieland, F. T. Science 272, 227–234 (1996).

    Article  CAS  PubMed  Google Scholar 

  2. Schekman, R. & Orci, L. Science 271, 1526–1533 (1996).

    Article  CAS  PubMed  Google Scholar 

  3. Girod, A. et al. Nature Cell Biol. 1, 423–430 (1999).

    Article  CAS  PubMed  Google Scholar 

  4. White, J. et al. J. Cell Biol. 147, 743–760 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Storrie, B., Pepperkok, R. & Nilsson, T. Trends Cell Biol. 10, 385–391 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. Martinez, O. et al. Proc. Natl Acad. Sci. USA 94, 1828–1833 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bullock, S. L. & Ish-Horowicz, D. Nature 414, 611–616 (2001).

    Article  CAS  PubMed  Google Scholar 

  8. Hoogenraad, C. C. et al. EMBO J. 20, 4041–4054 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Baens, M. & Marynen, P. Genomics 45, 601–606 (1997).

    Article  CAS  PubMed  Google Scholar 

  10. Swan, A., Nguyen, T. & Suter, B. Nature Cell Biol. 1, 444–449 (1999).

    Article  CAS  PubMed  Google Scholar 

  11. Johannes, L. & Goud, B. Trends Cell Biol. 8, 158–162 (1998).

    Article  CAS  PubMed  Google Scholar 

  12. Zerial, M. & McBride, H. Nature Rev. Mol. Cell Biol. 2, 107–117 (2001).

    Article  CAS  Google Scholar 

  13. Pfeffer, S. R. Trends Cell Biol. 11, 487–491 (2001).

    Article  CAS  PubMed  Google Scholar 

  14. Gross, S. P., Welte, M. A., Block, S. M. & Wieschaus, E. F. J. Cell Biol. 156, 715–724 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Echard, A. et al. Science 279, 580–585 (1998).

    Article  CAS  PubMed  Google Scholar 

  16. King, S. J. & Schroer, T. A. Nature Cell Biol. 2, 20–24 (2000).

    Article  CAS  PubMed  Google Scholar 

  17. Martinez, O. et al. J. Cell Biol. 127, 1575–1588 (1994).

    Article  CAS  PubMed  Google Scholar 

  18. Hoogenraad, C. C., Akhmanova, A., Grosveld, F., De Zeeuw, C. I. & Galjart, N. J. Cell Sci. 113, 2285–2297 (2000).

    CAS  PubMed  Google Scholar 

  19. Schiedel, A. C., Barnekow, A. & Mayer, T. FEBS Lett. 376, 113–119 (1995).

    Article  CAS  PubMed  Google Scholar 

  20. Johannes, L., Tenza, D., Antony, C. & Goud, B. J. Biol. Chem. 272, 19554–19561 (1997).

    Article  CAS  PubMed  Google Scholar 

  21. Elbashir, S. M. et al. Nature 411, 494–498 (2001).

    Article  CAS  PubMed  Google Scholar 

  22. Akhmanova, A. et al. Cell 104, 923–935 (2001).

    Article  CAS  PubMed  Google Scholar 

  23. Suter, B., Romberg, L. M. & Steward, R. Genes Dev. 3, 1957–1968 (1989).

    Article  CAS  PubMed  Google Scholar 

  24. Purcell, K. & Artavanis-Tsakonas, S. J. Cell Biol. 146, 731–740 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank I. G. Macara, S. R. Pfeffer, D. Gallwitz, E. G. Berger and H. P. Hauri for providing reagents. We also thank M. Rosing, K. Bilbilis, M. Koester, E. Ossendorf and A. Theil for experimental assistance. This research was supported by grants from the Netherlands Organisation for Scientific Research (ZonMw/900-00-001), the Erasmus University and grants from Fonds der Chemischen Industrie (FCI) and Deutsche Forschungsgemeinschaft (DFG) to A.B. This study contains major parts of the PhD thesis of T.M. T.M. is a fellow of the Graduiertenfoerderung of Nordrhein-Westfalen.

Author information

Author notes

  1. Casper C. Hoogenraad

    Present address: Picower Center for Learning and Memory, Massachusetts Institute of Technology, 77 Massachusetts Avenue (E18-215), Cambridge, MA 02139, USA

  2. Theodoros Matanis and Anna Akhmanova: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Experimental Tumorbiology, University of Muenster, Badestrasse 9, Muenster, D-48149, Germany

    Theodoros Matanis, Thomas Weide & Angelika Barnekow

  2. Department of Neuroscience, Erasmus University Rotterdam, P.O. Box 1738, Rotterdam, 3000, DR, The Netherlands

    Phebe Wulf, Chris I. De Zeeuw & Casper C. Hoogenraad

  3. Department of Cell Biology and Genetics, Erasmus University Rotterdam, P.O. Box 1738, Rotterdam, 3000, DR, The Netherlands

    Anna Akhmanova, Tatiana Stepanova, Niels Galjart & Frank Grosveld

  4. UMR CNRS 144, Institut Curie, 26 rue d'Ulm, Paris, 75248, Cedex 05, France

    Elaine Del Nery & Bruno Goud

Authors
  1. Theodoros Matanis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anna Akhmanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Phebe Wulf
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elaine Del Nery
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas Weide
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tatiana Stepanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Niels Galjart
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Frank Grosveld
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bruno Goud
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chris I. De Zeeuw
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Angelika Barnekow
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Casper C. Hoogenraad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Anna Akhmanova or Casper C. Hoogenraad.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information: Additional Materials and methods

Supplementary information: Tables (DOC 63 kb)

Figure S1

Specificity of the #2293 and #2296 antibodies using immunofluorescence microscopy and colocalisation between BICD proteins and Golgi markers (JPG 239 kb)

Figure S2

Silencing of Rab6 in HeLa cells. (JPG 1160 kb)

Figure S3

BICD2-C causes peripheral accumulation of COPI-independent Golgi-ER cargo, but has no effect on GM130 and γ-adaptin (JPG 1126 kb)

Figure S4

BICD2-C has no effect on the microtubule network and induces no accumulation of dynein or dynactin. (JPG 713 kb)

Movie 1

GFP-Rab6A movement in HeLa cells (AVI 903 kb)

Movie 2

GFP-Rab6A movement in HeLa cells expressing BICD2-C (AVI 796 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Matanis, T., Akhmanova, A., Wulf, P. et al. Bicaudal-D regulates COPI-independent Golgi–ER transport by recruiting the dynein–dynactin motor complex. Nat Cell Biol 4, 986–992 (2002). https://doi.org/10.1038/ncb891

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb891

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