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:

Membrane curvature enables N-Ras lipid anchor sorting to liquid-ordered membrane phases

Nature Chemical Biology volume 11, pages 192–194 (2015)Cite this article

Subjects

Abstract

Trafficking and sorting of membrane-anchored Ras GTPases are regulated by partitioning between distinct membrane domains. Here, in vitro experiments and microscopic molecular theory reveal membrane curvature as a new modulator of N-Ras lipid anchor and palmitoyl chain partitioning. Membrane curvature was essential for enrichment in raft-like liquid-ordered phases; enrichment was driven by relief of lateral pressure upon anchor insertion and most likely affects the localization of lipidated proteins in general.

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: Membrane curvature enables the association of tN-Ras and palmitoyl anchors with lo membrane phases.
Figure 2: Increased relief of the lateral pressure in curved lo versus ld membranes as the underlying mechanism for preferential lo partitioning of lipidated moieties in highly curved membranes.

Similar content being viewed by others

References

  1. Cox, A.D. & Der, C. Small GTPases 1, 2–27 (2010).

    Article  Google Scholar 

  2. Hancock, J.F. Nat. Rev. Mol. Cell Biol. 4, 373–384 (2003).

    Article  CAS  Google Scholar 

  3. Belanis, L., Plowman, S.J., Rotblat, B., Hancock, J.F. & Kloog, Y. Mol. Biol. Cell 19, 1404–1414 (2008).

    Article  CAS  Google Scholar 

  4. Hancock, J.F. & Parton, R.G. Biochem. J. 389, 1–11 (2005).

    Article  CAS  Google Scholar 

  5. Prior, I.A. et al. Nat. Cell Biol. 3, 368–375 (2001).

    Article  CAS  Google Scholar 

  6. Yan, J., Roy, S., Apolloni, A., Lane, A. & Hancock, J.F. J. Biol. Chem. 273, 24052–24056 (1998).

    Article  CAS  Google Scholar 

  7. Weise, K., Triola, G., Brunsveld, L., Waldmann, H. & Winter, R. J. Am. Chem. Soc. 131, 1557–1564 (2009).

    Article  CAS  Google Scholar 

  8. Johnson, S.A. et al. Biochim. Biophys. Acta 1798, 1427–1435 (2010).

    Article  CAS  Google Scholar 

  9. Nicolini, C. et al. J. Am. Chem. Soc. 128, 192–201 (2006).

    Article  CAS  Google Scholar 

  10. Simons, K. & Gerl, M.J. Nat. Rev. Mol. Cell Biol. 11, 688–699 (2010).

    Article  CAS  Google Scholar 

  11. Anderson, R.G.W. Annu. Rev. Biochem. 67, 199–225 (1998).

    Article  CAS  Google Scholar 

  12. Kunding, A.H., Mortensen, M.W., Christensen, S.M. & Stamou, D. Biophys. J. 95, 1176–1188 (2008).

    Article  CAS  Google Scholar 

  13. Bendix, P.M., Pedersen, M.S. & Stamou, D. Proc. Natl. Acad. Sci. USA 106, 12341–12346 (2009).

    Article  CAS  Google Scholar 

  14. Hatzakis, N.S. et al. Nat. Chem. Biol. 5, 835–841 (2009).

    Article  CAS  Google Scholar 

  15. Kamal, M.M., Mills, D., Grzybek, M. & Howard, J. Proc. Natl. Acad. Sci. USA 106, 22245–22250 (2009).

    Article  CAS  Google Scholar 

  16. Roux, A. et al. EMBO J. 24, 1537–1545 (2005).

    Article  CAS  Google Scholar 

  17. Vamparys, L. et al. Biophys. J. 104, 585–593 (2013).

    Article  CAS  Google Scholar 

  18. Meinhardt, S., Vink, R.L.C. & Schmid, F. Proc. Natl. Acad. Sci. USA 110, 4476–4481 (2013).

    Article  CAS  Google Scholar 

  19. Cui, H., Lyman, E. & Voth, G.A. Biophys. J. 100, 1271–1279 (2011).

    Article  CAS  Google Scholar 

  20. Uline, M.J., Longo, G.S., Schick, M. & Szleifer, I. Biophys. J. 98, 1883–1892 (2010).

    Article  CAS  Google Scholar 

  21. Sampaio, J.L., Moreno, M.J. & Vaz, W.L.C. Biophys. J. 88, 4064–4071 (2005).

    Article  CAS  Google Scholar 

  22. Abreu, M.S.C., Moreno, M.J. & Vaz, W.L.C. Biophys. J. 87, 353–365 (2004).

    Article  CAS  Google Scholar 

  23. Sezgin, E. et al. Biochim. Biophys. Acta 1818, 1777–1784 (2012).

    Article  CAS  Google Scholar 

  24. Parthasarathy, R., Yu, C.H. & Groves, J.T. Langmuir 22, 5095–5099 (2006).

    Article  CAS  Google Scholar 

  25. Baumgart, T., Hess, S.T. & Webb, W.W. Nature 425, 821–824 (2003).

    Article  CAS  Google Scholar 

  26. Shahinian, S. & Silvius, J.R. Biochemistry 34, 3813–3822 (1995).

    Article  CAS  Google Scholar 

  27. Chiu, V.K. et al. J. Biol. Chem. 279, 7346–7352 (2004).

    Article  CAS  Google Scholar 

  28. Hughes, L.D., Rawle, R.J. & Boxer, S.G. PLoS ONE 9, e87649 (2014).

    Article  Google Scholar 

  29. Veatch, S.L. & Keller, S.L. Biochim. Biophys. Acta. 1746, 172–185 (2005).

    Article  CAS  Google Scholar 

  30. Bhatia, V.K. et al. EMBO J. 28, 3303–3314 (2009).

    Article  CAS  Google Scholar 

  31. Bhatia, V.K., Hatzakis, N.S. & Stamou, D. Semin. Cell Dev. Biol. 21, 381–390 (2010).

    Article  CAS  Google Scholar 

  32. Rocks, O. et al. Science 307, 1746–1752 (2005).

    Article  CAS  Google Scholar 

  33. Larsen, J., Hatzakis, N.S. & Stamou, D. J. Am. Chem. Soc. 133, 10685–10687 (2011).

    Article  CAS  Google Scholar 

  34. Elizondo, E. et al. J. Am. Chem. Soc. 134, 1918–1921 (2012).

    Article  CAS  Google Scholar 

  35. Silvius, J.R. Biochim. Biophys. Acta. 1746, 193–202 (2005).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Lundbeck Foundation Center for Biomembranes in Nanomedicine, the Danish Councils for Independent and Strategic Research and the University of Copenhagen programs of excellence, 'Single-Molecule Nanoscience', 'BioScaRT' and 'UNIK-Synthetic Biology'. I.S. would like to acknowledge support from the U.S. National Science Foundation under grant no. CBET-1403058, and M.J.U acknowledges support from the US National Institutes of Health under grant no. P20GM103499.

Author information

Author notes

  1. Martin Borch Jensen, Vikram K Bhatia & Søren L Pedersen

    Present address: Present addresses: The Buck Institute for Research on Aging, Novato, California, USA (M.B.J.); Novozymes A/S, Bagsvaerd, Denmark (V.K.B.); Gubra ApS, Hørsholm, Denmark (S.L.P.).,

Authors and Affiliations

  1. Bio-Nanotechnology and Nanomedicine Laboratory, Nano-Science Center, University of Copenhagen, Denmark

    Jannik Bruun Larsen, Martin Borch Jensen, Vikram K Bhatia, Thomas Bjørnholm, Lars Iversen, Nikos S Hatzakis & Dimitrios Stamou

  2. Department of Chemistry, University of Copenhagen, Denmark

    Jannik Bruun Larsen, Martin Borch Jensen, Vikram K Bhatia, Søren L Pedersen, Lars Iversen, Knud J Jensen, Nikos S Hatzakis & Dimitrios Stamou

  3. Lundbeck Foundation Center for Biomembranes in Nanomedicine, University of Copenhagen, Denmark

    Jannik Bruun Larsen, Martin Borch Jensen, Vikram K Bhatia, Søren L Pedersen, Lars Iversen, Knud J Jensen, Nikos S Hatzakis & Dimitrios Stamou

  4. Department of Chemical Engineering, University of South Carolina, Columbia, South Carolina, USA

    Mark Uline

  5. Department of Biomedical Engineering, Department of Chemistry and Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois, USA

    Igal Szleifer

Authors
  1. Jannik Bruun Larsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martin Borch Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vikram K Bhatia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Søren L Pedersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas Bjørnholm
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lars Iversen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mark Uline
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Igal Szleifer
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Knud J Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Nikos S Hatzakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Dimitrios Stamou
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

D.S. conceived the strategy and was responsible for the overall project management. D.S., N.S.H., J.B.L. and M.B.J designed all experiments, which were performed by J.B.L. and M.B.J with help from N.S.H. and V.K.B. S.L.P. and K.J.J. synthesized and purified tN-Ras. M.J.U. and I.S. performed theoretical calculations of anchor partitioning. J.B.L., D.S., L.I. and N.S.H. wrote the manuscript. D.S. and N.S.H. supervised the project. All authors discussed the results and commented on the manuscript at all stages.

Corresponding author

Correspondence to Dimitrios Stamou.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Results and Supplementary Figures 1–14. (PDF 4117 kb)

Supplementary Note

Supplementary Note (PDF 781 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Larsen, J., Jensen, M., Bhatia, V. et al. Membrane curvature enables N-Ras lipid anchor sorting to liquid-ordered membrane phases. Nat Chem Biol 11, 192–194 (2015). https://doi.org/10.1038/nchembio.1733

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio.1733

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