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:

Exo70 interacts with the Arp2/3 complex and regulates cell migration

Nature Cell Biology volume 8, pages 1383–1388 (2006)Cite this article

Abstract

The exocyst is a multiprotein complex essential for tethering secretory vesicles to specific domains of the plasma membrane for exocytosis1,2,3. Here, we report that the exocyst component Exo70 interacts with the Arp2/3 complex, a key regulator of actin polymerization4,5. We further show that the exocyst–Arp2/3 interaction is regulated by epidermal growth factor (EGF) signalling. Inhibition of Exo70 by RNA interference (RNAi) or antibody microinjection blocks the formation of actin-based membrane protrusions and affects various aspects of cell motility. We propose that Exo70, in addition to functioning in exocytosis, also regulates actin at the leading edges of migrating cells, therefore coordinating cytoskeleton and membrane traffic during cell migration.

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: Exo70 interacts with the Arp2/3 complex.
Figure 2: Exo70 regulates cell migration (a) Immunolocalization of Exo70 (red) and Arp2 (green) to the leading edges of migrating NRK cells in a wound-healing assay.
Figure 3: The C-terminus of Exo70 is necessary for its ability to induce membrane protusions.
Figure 4: Exo70 is necessary for the generation of actin-based membrane protrusions.
Figure 5: Regulation of the interaction between the exocyst and Arp2/3 by EGF.

Similar content being viewed by others

References

  1. Novick, P. & Guo, W. Ras family therapy: Rab, Rho and Ral talk to the exocyst. Trends Cell Biol. 12, 247–249 (2002).

    Article  CAS  Google Scholar 

  2. Lipschutz, J. & Mostov, K. Exocytosis: the many masters of the exocyst. Curr. Biol. 12, R212–R214 (2002).

    Article  CAS  Google Scholar 

  3. Hsu, S-C, TerBush, D., Abraham, M. & Guo, W. The exocyst complex in polarized exocytosis. Int. Rev. Cytol. 233, 243–265 (2004).

    Article  CAS  Google Scholar 

  4. Pollard, T. D., Borisy, G. G. Cellular motility driven by assembly and disassembly of actin filaments. Cell 112, 453–465 (2003).

    Article  CAS  Google Scholar 

  5. Ridley, A. J. et al. Cell migration: integrating signals from front to back. Science 302, 1704–1709 (2003).

    Article  CAS  Google Scholar 

  6. Bretscher, M. S. Getting membrane flow and the cytoskeleton to cooperate in moving cells. Cell 87, 601–606 (1996).

    Article  CAS  Google Scholar 

  7. Wang, S. et al. The mammalian exocyst, a complex required for exocytosis, inhibits tubulin polymerization. J. Biol. Chem. 279, 35958–35966 (2004).

    Article  CAS  Google Scholar 

  8. Xu, K. F. et al. Interaction of BIG2, a brefeldin A-inhibited guanine nucleotide-exchange protein, with exocyst protein Exo70. Proc. Natl Acad. Sc.i USA 102, 2784–2789 (2005).

    Article  CAS  Google Scholar 

  9. Rosse, C. et al. RalB mobilizes the exocyst to drive cell migration. Mol. Cell Biol. 26, 727–734 (2006).

    Article  CAS  Google Scholar 

  10. Sugihara, K. et al. The exocyst complex binds the small GTPase RalA to mediate filopodia formation. Nature Cell Biol. 4, 73–78 (2002).

    Article  CAS  Google Scholar 

  11. Takaya, A., Ohba, Y., Kurokawa, K. & Matsuda, M. RalA activation at nascent lamellipodia of epidermal growth factor-stimulated Cos7 cells and migrating Madin-Darby canine kidney cells. Mol. Biol. Cell 15, 2549–2557 (2004).

    Article  CAS  Google Scholar 

  12. Welch, M. D., DePace, A. H., Verma, S., Iwamatsu, A. & Mitchison, T. J. The human Arp2/3 complex is composed of evolutionarily conserved subunits and is localized to cellular regions of dynamic actin filament assembly. J. Cell Biol. 138, 375–384 (1997).

    Article  CAS  Google Scholar 

  13. Machesky, L. M. et al. Mammalian actin-related protein 2/3 complex localizes to regions of lamellipodial protrusion and is composed of evolutionarily conserved proteins. Biochem. J. 328, 105–112 (1997).

    Article  CAS  Google Scholar 

  14. Machesky, L. M. & Insall, R. H. Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex. Curr. Biol. 8, 1347–1356 (1998).

    Article  CAS  Google Scholar 

  15. Marchand, J. B., Kaiser, D. A., Pollard, T. D. & Higgs, H. N. Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3 complex. Nature Cell Biol. 3, 76–82 (2001).

    Article  CAS  Google Scholar 

  16. Inoue, M., Chang, L., Hwang, J., Chiang, S. H. & Saltiel, A. R. The exocyst complex is required for targeting of Glut4 to the plasma membrane by insulin. Nature 422, 629–633 (2003).

    Article  CAS  Google Scholar 

  17. Nobes, C. D. & Hall, A. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81, 53–62 (1995).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank T. Svitkina, M. Welch, B. Goode, S. Zigmond, M. Chou, J. Peterson and C. Yang for reagents and numerous constructive discussions during the research. This work is supported by the National Institutes of Health (NIH), the American Cancer Society (ACS), the American Heart Association (AHA) and the Pew Scholars Program for Biomedical Sciences to W.G.

Author information

Authors and Affiliations

  1. Department of Biology, University of Pennsylvania, Philadelphia, 19104, PA, USA

    Xiaofeng Zuo, Jian Zhang & Wei Guo

  2. Department of Biological Sciences, Purdue University, West Lafayette, 47907, IN, USA

    Ying Zhang & Daoguo Zhou

  3. Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, 08854, NJ, USA

    Shu-Chan Hsu

Authors
  1. Xiaofeng Zuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shu-Chan Hsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daoguo Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wei Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei Guo.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary figures S1, S2 and Supplementary materials (PDF 291 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zuo, X., Zhang, J., Zhang, Y. et al. Exo70 interacts with the Arp2/3 complex and regulates cell migration. Nat Cell Biol 8, 1383–1388 (2006). https://doi.org/10.1038/ncb1505

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb1505

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