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:

Direct visualization of specifically modified extracellular glycans in living animals

Nature Methods volume 9, pages 477–479 (2012)Cite this article

Subjects

Abstract

Modification patterns of heparan sulfate coordinate protein function in metazoans, yet in vivo imaging of such non–genetically encoded structures has been impossible. Here we report a transgenic method in Caenorhabditis elegans that allows direct live imaging of specific heparan sulfate modification patterns. This experimental approach reveals a dynamic and cell-specific heparan sulfate landscape and could in principle be adapted to visualize and analyze any extracellular molecule in vivo.

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: A technique to visualize specifically modified heparan sulfate in vivo.
Figure 2: Distinct subcellular heparan sulfate modification patterns.

Similar content being viewed by others

References

  1. Wang, S. & Hazelrigg, T. Nature 369, 400–403 (1994).

    Article  CAS  PubMed  Google Scholar 

  2. Laughlin, S.T., Baskin, J.M., Amacher, S.L. & Bertozzi, C.R. Science 320, 664–667 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Laughlin, S.T. & Bertozzi, C.R. ACS Chem. Biol. 4, 1068–1072 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bishop, J.R., Schuksz, M. & Esko, J.D. Nature 446, 1030–1037 (2007).

    Article  CAS  PubMed  Google Scholar 

  5. Bülow, H.E. & Hobert, O. Annu. Rev. Cell Dev. Biol. 22, 375–407 (2006).

    Article  PubMed  Google Scholar 

  6. Holt, C.E. & Dickson, B.J. Neuron 46, 169–172 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. van Kuppevelt, T.H., Dennissen, M.A., van Venrooij, W.J., Hoet, R.M. & Veerkamp, J.H. J. Biol. Chem. 273, 12960–12966 (1998).

    Article  CAS  PubMed  Google Scholar 

  8. Ten Dam, G.B. et al. J. Biol. Chem. 281, 4654–4662 (2006).

    Article  CAS  PubMed  Google Scholar 

  9. Smits, N.C. et al. Methods Enzymol. 416, 61–87 (2006).

    Article  CAS  PubMed  Google Scholar 

  10. Townley, R.A. & Bülow, H.E. J. Biol. Chem. 286, 16824–16831 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lieleg, O., Baumgärtel, R.M. & Bausch, A.R. Biophys. J. 97, 1569–1577 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hall, D.H. & Altun, Z.F. Muscle System. in C. elegans Atlas 145–188 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2008).

  13. Jenniskens, G.J. et al. FASEB J. 17, 878–880 (2003).

    Article  CAS  PubMed  Google Scholar 

  14. Dennissen, M.A. et al. J. Biol. Chem. 277, 10982–10986 (2002).

    Article  CAS  PubMed  Google Scholar 

  15. Kurup, S. et al. J. Biol. Chem. 282, 21032–21042 (2007).

    Article  CAS  PubMed  Google Scholar 

  16. van de Westerlo, E.M. et al. Blood 99, 2427–2433 (2002).

    Article  CAS  PubMed  Google Scholar 

  17. Brenner, S. Genetics 77, 71–94 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Bénard, C., Tjoe, N., Boulin, T., Recio, J. & Hobert, O. Genetics 183, 917–927 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  19. van Kuppevelt, T.H., Dennissen, M.A., van Venrooij, W.J., Hoet, R.M. & Veerkamp, J.H. J. Biol. Chem. 273, 12960–12966 (1998).

    Article  CAS  PubMed  Google Scholar 

  20. Fares, H. & Greenwald, I. Genetics 159, 133–145 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Grant, B. & Greenwald, I. Development 124, 637–644 (1997).

    CAS  PubMed  Google Scholar 

  22. Loria, P.M., Hodgkin, J. & Hobert, O. J. Neurosci. 24, 2191–2201 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hermann, G.J. et al. Mol. Biol. Cell 16, 3273–3288 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hobert, O. Biotechniques 32, 728–730 (2002).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank J. Attonito, N. Gomez and P. Weinberg for technical assistance, H. Fares (University of Arizona, Tucson) for providing the pJF33 plasmid, E. Snapp (Albert Einstein College of Medicine) for the superfolder GFP plasmid, S. Mitani (Tokyo Women's Medical University School of Medicine) for providing the tm734, tm3006 and tm3208 alleles of heparan 3O-sulfotransferases, and L. Attreed, S. Emmons, O. Hobert and members of the Bülow laboratory for comments on the manuscript. This work was supported in part by grants from the US National Institutes of Health (5R01HD055380 and RC1GM090825 to H.E.B.; T32 GM007491 to M.A.). H.E.B. is funded as an Alfred P. Sloan fellow.

Author information

Authors and Affiliations

  1. Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, USA

    Matthew Attreed, Muriel Desbois & Hannes E Bülow

  2. Department of Biochemistry, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

    Toin H van Kuppevelt

  3. Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA

    Hannes E Bülow

Authors
  1. Matthew Attreed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Muriel Desbois
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toin H van Kuppevelt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hannes E Bülow
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.A. conducted all experiments. M.D. constructed several transgenic strains and important constructs. T.H.v.K. contributed vsv-tagged scFv antibody preparations. M.A. and H.E.B. analyzed data and wrote the manuscript with editorial input from M.D. and T.H.v.K.

Corresponding author

Correspondence to Hannes E Bülow.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–12 (PDF 5473 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Attreed, M., Desbois, M., van Kuppevelt, T. et al. Direct visualization of specifically modified extracellular glycans in living animals. Nat Methods 9, 477–479 (2012). https://doi.org/10.1038/nmeth.1945

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmeth.1945

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