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 calcium-dependent acyltransferase that produces N-acyl phosphatidylethanolamines

Nature Chemical Biology volume 12, pages 669–671 (2016)Cite this article

Subjects

Abstract

More than 30 years ago, a calcium-dependent enzyme activity was described that generates N-acyl phosphatidylethanolamines (NAPEs), which are precursors for N-acyl ethanolamine (NAE) lipid transmitters, including the endocannabinoid anandamide. The identity of this calcium-dependent N-acyltransferase (Ca-NAT) has remained mysterious. Here, we use activity-based protein profiling to identify the poorly characterized serine hydrolase PLA2G4E as a mouse brain Ca-NAT and show that this enzyme generates NAPEs and NAEs in mammalian cells.

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: Characterization of Ca-NAT activity in mouse brain.
Figure 2: Recombinant PLA2G4E exhibits Ca-NAT activity and generates NAPEs and NAEs in mammalian cells.

Similar content being viewed by others

Accession codes

Accessions

NCBI Reference Sequence

References

  1. Petrosino, S., Ligresti, A. & Di Marzo, V. Curr. Opin. Chem. Biol. 13, 309–320 (2009).

    Article  CAS  Google Scholar 

  2. Rahman, I.A., Tsuboi, K., Uyama, T. & Ueda, N. Pharmacol. Res. 86, 1–10 (2014).

    Article  CAS  Google Scholar 

  3. Blankman, J.L. & Cravatt, B.F. Pharmacol. Rev. 65, 849–871 (2013).

    Article  Google Scholar 

  4. Wellner, N., Diep, T.A., Janfelt, C. & Hansen, H.S. Biochim. Biophys. Acta 1831, 652–662 (2013).

    Article  CAS  Google Scholar 

  5. Okamoto, Y., Morishita, J., Tsuboi, K., Tonai, T. & Ueda, N. J. Biol. Chem. 279, 5298–5305 (2004).

    Article  CAS  Google Scholar 

  6. Simon, G.M. & Cravatt, B.F. Mol. Biosyst. 6, 1411–1418 (2010).

    Article  CAS  Google Scholar 

  7. Sun, Y.X. et al. Biochem. J. 380, 749–756 (2004).

    Article  CAS  Google Scholar 

  8. Liu, J. et al. Proc. Natl. Acad. Sci. USA 103, 13345–13350 (2006).

    Article  CAS  Google Scholar 

  9. Reddy, P.V., Natarajan, V., Schmid, P.C. & Schmid, H.H. Biochim. Biophys. Acta 750, 472–480 (1983).

    Article  CAS  Google Scholar 

  10. Natarajan, V., Schmid, P.C., Reddy, P.V., Zuzarte-Augustin, M.L. & Schmid, H.H.O. J. Neurochem. 41, 1303–1312 (1983).

    Article  CAS  Google Scholar 

  11. Cadas, H., di Tomaso, E. & Piomelli, D. J. Neurosci. 17, 1226–1242 (1997).

    Article  CAS  Google Scholar 

  12. Cadas, H., Gaillet, S., Beltramo, M., Venance, L. & Piomelli, D. J. Neurosci. 16, 3934–3942 (1996).

    Article  CAS  Google Scholar 

  13. Uyama, T. et al. J. Biol. Chem. 287, 31905–31919 (2012).

    Article  CAS  Google Scholar 

  14. Piper, D.E. et al. J. Lipid Res. 56, 1711–1719 (2015).

    Article  CAS  Google Scholar 

  15. Niphakis, M.J. & Cravatt, B.F. Annu. Rev. Biochem. 83, 341–377 (2014).

    Article  CAS  Google Scholar 

  16. Ohto, T., Uozumi, N., Hirabayashi, T. & Shimizu, T. J. Biol. Chem. 280, 24576–24583 (2005).

    Article  CAS  Google Scholar 

  17. Ghosh, M., Tucker, D.E., Burchett, S.A. & Leslie, C.C. Prog. Lipid Res. 45, 487–510 (2006).

    Article  CAS  Google Scholar 

  18. Ghomashchi, F. et al. J. Biol. Chem. 285, 36100–36111 (2010).

    Article  CAS  Google Scholar 

  19. Natarajan, V., Schmid, P.C. & Schmid, H.H.O. Biochim. Biophys. Acta 878, 32–41 (1986).

    Article  CAS  Google Scholar 

  20. Moesgaard, B., Petersen, G., Jaroszewski, J.W. & Hansen, H.S. J. Lipid Res. 41, 985–990 (2000).

    CAS  PubMed  Google Scholar 

  21. Shinohara, N. et al. J. Lipid Res. 52, 1927–1935 (2011).

    Article  CAS  Google Scholar 

  22. Jin, X.H. et al. J. Biol. Chem. 282, 3614–3623 (2007).

    Article  CAS  Google Scholar 

  23. Viader, A. et al. eLife 5 doi: 10.7554/eLife.12345 (2016).

  24. Zhang, Y. et al. J. Neurosci. 34, 11929–11947 (2014).

    Article  CAS  Google Scholar 

  25. Simon, G.M. & Cravatt, B.F. J. Biol. Chem. 281, 26465–26472 (2006).

    Article  CAS  Google Scholar 

  26. Simon, G.M. & Cravatt, B.F. J. Biol. Chem. 283, 9341–9349 (2008).

    Article  CAS  Google Scholar 

  27. Lee, H.C., Simon, G.M. & Cravatt, B.F. Biochemistry 54, 2539–2549 (2015).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to H.Y. Lee for assistance with enzyme assays and G. Simon for numerous helpful discussions and critical reading of the manuscript. This work was supported by the US National Institutes of Health (DA033760), a Hewitt Foundation for Medical Research Fellowship (to W.H.P.) and the ninth Irving S. Sigal Postdoctoral Fellowship from the American Chemical Society (to S.S.K.).

Author information

Authors and Affiliations

  1. Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA

    Yuji Ogura, William H Parsons, Siddhesh S Kamat & Benjamin F Cravatt

  2. The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA

    Yuji Ogura, William H Parsons, Siddhesh S Kamat & Benjamin F Cravatt

Authors
  1. Yuji Ogura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William H Parsons
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Siddhesh S Kamat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Benjamin F Cravatt
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Y.O. and B.F.C. conceived the project. Y.O., W.H.P., S.S.K. and B.F.C. designed experiments. Y.O. characterized Ca-NAT activity in brain and performed the correlation profiling. Y.O., W.H.P. and S.S.K. characterized the activity of heterologously expressed PLA2G4E and performed the feeding studies. Y.O. and B.F.C. wrote the paper. W.H.P. edited the paper.

Corresponding author

Correspondence to Benjamin F Cravatt.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Results and Supplementary Figures 1–13. (PDF 7767 kb)

Supplementary Table 1

Complete ABPP-MudPIT data set. (XLSX 99 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ogura, Y., Parsons, W., Kamat, S. et al. A calcium-dependent acyltransferase that produces N-acyl phosphatidylethanolamines. Nat Chem Biol 12, 669–671 (2016). https://doi.org/10.1038/nchembio.2127

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio.2127

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