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:

A fluorescent probe for cysteine depalmitoylation reveals dynamic APT signaling

Nature Chemical Biology volume 13, pages 150–152 (2017)Cite this article

Subjects

Abstract

Hundreds of human proteins are modified by reversible palmitoylation of cysteine residues (S-palmitoylation), but the regulation of depalmitoylation is poorly understood. Here, we develop 'depalmitoylation probes' (DPPs), small-molecule fluorophores, to monitor the endogenous activity levels of 'erasers' of S-palmitoylation, acylprotein thioesterases (APTs). Live-cell analysis with DPPs reveals rapid growth-factor-mediated inhibition of the depalmitoylation activity of APTs, exposing a novel regulatory mechanism of dynamic lipid signaling.

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: Design and in vitro validation of DPPs.
Figure 2: Analysis of endogenous and growth-factor-stimulated depalmitoylase activities using DPPs.

Similar content being viewed by others

References

  1. Linder, M.E. & Deschenes, R.J. Nat. Rev. Mol. Cell Biol. 8, 74–84 (2007).

    Article  CAS  Google Scholar 

  2. Eisenberg, S. et al. Biochem. Soc. Trans. 41, 79–83 (2013).

    Article  CAS  Google Scholar 

  3. Topinka, J.R. & Bredt, D.S. Neuron 20, 125–134 (1998).

    Article  CAS  Google Scholar 

  4. Chan, P. et al. Nat. Chem. Biol. 12, 282–289 (2016).

    Article  CAS  Google Scholar 

  5. Peng, T., Thinon, E. & Hang, H.C. Curr. Opin. Chem. Biol. 30, 77–86 (2016).

    Article  CAS  Google Scholar 

  6. Hernandez, J.L., Majmudar, J.D. & Martin, B.R. Curr. Opin. Chem. Biol. 17, 20–26 (2013).

    Article  CAS  Google Scholar 

  7. Zheng, B. et al. J. Am. Chem. Soc. 135, 7082–7085 (2013).

    Article  CAS  Google Scholar 

  8. Verkruyse, L.A. & Hofmann, S.L. J. Biol. Chem. 271, 15831–15836 (1996).

    Article  CAS  Google Scholar 

  9. Long, J.Z. & Cravatt, B.F. Chem. Rev. 111, 6022–6063 (2011).

    Article  CAS  Google Scholar 

  10. Lin, D.T. & Conibear, E. eLife 4, e11306 (2015).

    Article  Google Scholar 

  11. Rocks, O. et al. Cell 141, 458–471 (2010).

    Article  CAS  Google Scholar 

  12. El-Husseini Ael, D. et al. Cell 108, 849–863 (2002).

    Article  Google Scholar 

  13. Ponimaskin, E. et al. J. Neurosci. 28, 8897–8907 (2008).

    Article  CAS  Google Scholar 

  14. Zhang, M.M., Tsou, L.K., Charron, G., Raghavan, A.S. & Hang, H.C. Proc. Natl. Acad. Sci. USA 107, 8627–8632 (2010).

    Article  CAS  Google Scholar 

  15. Kong, E. et al. J. Biol. Chem. 288, 9112–9125 (2013).

    Article  CAS  Google Scholar 

  16. Davda, D. & Martin, B.R. MedChemComm 5, 268–276 (2014).

    Article  CAS  Google Scholar 

  17. Dekker, F.J. et al. Nat. Chem. Biol. 6, 449–456 (2010).

    Article  CAS  Google Scholar 

  18. Rusch, M. et al. Angew. Chem. Int. Edn Engl. 50, 9838–9842 (2011).

    Article  CAS  Google Scholar 

  19. Adibekian, A. et al. J. Am. Chem. Soc. 134, 10345–10348 (2012).

    Article  CAS  Google Scholar 

  20. Görmer, K. et al. ChemBioChem 13, 1017–1023 (2012).

    Article  Google Scholar 

  21. Creaser, S.P. & Peterson, B.R. J. Am. Chem. Soc. 124, 2444–2445 (2002).

    Article  CAS  Google Scholar 

  22. Lee, J.H., Lim, C.S., Tian, Y.S., Han, J.H. & Cho, B.R. J. Am. Chem. Soc. 132, 1216–1217 (2010).

    Article  CAS  Google Scholar 

  23. Dekker, F.J. & Hedberg, C. Bioorg. Med. Chem. 19, 1376–1380 (2011).

    Article  CAS  Google Scholar 

  24. Paulsen, C.E. & Carroll, K.S. Chem. Rev. 113, 4633–4679 (2013).

    Article  CAS  Google Scholar 

  25. Lin, H., Su, X. & He, B. ACS Chem. Biol. 7, 947–960 (2012).

    Article  CAS  Google Scholar 

  26. Sauers, R.R., Husain, S.N., Piechowski, A.P. & Bird, G.R. Dyes Pigm. 8, 35–53 (1987).

    Article  CAS  Google Scholar 

  27. Smith, G.A., Metcalfe, J.C. & Clarke, S.D. J. Chem. Soc. Perkin Trans. 2 1993, 1195–1204 (1993).

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the University of Chicago, the National Institute of General Medical Sciences of the National Institutes of Health (R35 GM119840) to B.C.D., the University of Chicago Medicine Comprehensive Cancer Center (P30CA14599), and a “Catalyst Award” to B.C.D. from the Chicago Biomedical Consortium, with support from the Searle Funds at The Chicago Community Trust. We thank J. Pu (University of Chicago) and D. Dammeier (University of Chicago) for technical assistance, and C. He (University of Chicago), A. Mukherje (National Institutes of Health), Y. Krishnan (University of Chicago), and J. Lewis (University of Chicago) for supplying materials and equipment.

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Chicago, Chicago, Illinois, USA

    Rahul S Kathayat, Pablo D Elvira & Bryan C Dickinson

Authors
  1. Rahul S Kathayat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pablo D Elvira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bryan C Dickinson
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

R.S.K. and P.D.E. synthesized all compounds in the paper. R.S.K. performed all analytical measurements, in vitro assays, and cell culture experiments. R.S.K. and B.C.D. designed experimental strategies and wrote the paper.

Corresponding author

Correspondence to Bryan C Dickinson.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Results and Supplementary Figures 1–17. (PDF 4117 kb)

Supplementary Note

Synthetic Procedures. (PDF 1604 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kathayat, R., Elvira, P. & Dickinson, B. A fluorescent probe for cysteine depalmitoylation reveals dynamic APT signaling. Nat Chem Biol 13, 150–152 (2017). https://doi.org/10.1038/nchembio.2262

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio.2262

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