Abstract

Photoactivatable pharmacological agents have revolutionized neuroscience, but the palette of available compounds is limited. We describe a general method for caging tertiary amines by using a stable quaternary ammonium linkage that elicits a red shift in the activation wavelength. We prepared a photoactivatable nicotine (PA-Nic), uncageable via one- or two-photon excitation, that is useful to study nicotinic acetylcholine receptors (nAChRs) in different experimental preparations and spatiotemporal scales.

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References

  1. 1.

    et al. Nat. Neurosci. 4, 1086–1092 (2001).

  2. 2.

    Nat. Methods 4, 619–628 (2007).

  3. 3.

    , , & Nat. Chem. Biol. 6, 255–257 (2010).

  4. 4.

    et al. Proc. Natl. Acad. Sci. USA 96, 1193–1200 (1999).

  5. 5.

    et al. Angew. Chem. Int. Ed. Engl. 44, 7887–7891 (2005).

  6. 6.

    et al. Chemistry 14, 1621–1627 (2008).

  7. 7.

    , & J. Photochem. Photobiol. Chem. 117, 67–74 (1998).

  8. 8.

    , , , & J. Am. Chem. Soc. 124, 12662–12663 (2002).

  9. 9.

    , , & Bioorg. Med. Chem. Lett. 23, 2395–2398 (2013).

  10. 10.

    et al. J. Am. Chem. Soc. 139, 12591–12600 (2017).

  11. 11.

    , & J. Inorg. Biochem. 104, 1248–1251 (2010).

  12. 12.

    et al. J. Neurosci. 34, 9789–9802 (2014).

  13. 13.

    et al. Neuron 69, 445–452 (2011).

  14. 14.

    , , & J. Neurosci. 29, 3014–3018 (2009).

  15. 15.

    , & Mol. Pharmacol. 88, 1035–1044 (2015).

  16. 16.

    et al. Nature 499, 295–300 (2013).

  17. 17.

    , , , & J. Neurosci. 23, 9024–9031 (2003).

  18. 18.

    , , & Neuron 56, 141–154 (2007).

  19. 19.

    et al. Nat. Methods 13, 985–988 (2016).

  20. 20.

    & Synlett. 501–504 (2003).

  21. 21.

    , , & Biochemistry 46, 5479–5484 (2007).

  22. 22.

    et al. ChemBioChem 13, 1458–1464 (2012).

  23. 23.

    , , , & ChemBioChem 14, 2277–2283 (2013).

  24. 24.

    et al. Nat. Commun. 6, 10056 (2015).

  25. 25.

    & J. Opt. Soc. Am. B 13, 481–491 (1996).

  26. 26.

    , & Opt. Express 16, 4029–4047 (2008).

  27. 27.

    et al. Biophys. J. 102, 934–944 (2012).

  28. 28.

    et al. Nat. Methods 12, 244–250 (2015).

  29. 29.

    et al. J. Org. Chem. 74, 1721–1729 (2009).

  30. 30.

    et al. J. Biol. Chem. 280, 80–87 (2005).

  31. 31.

    et al. FASEB J. 24, 5113–5123 (2010).

  32. 32.

    et al. Cell Metab. 13, 195–204 (2011).

  33. 33.

    et al. Nat. Neurosci. 13, 133–140 (2010).

  34. 34.

    et al. Neuron 71, 995–1013 (2011).

  35. 35.

    et al. Nat. Commun. 6, 6770 (2015).

  36. 36.

    , & J. Vis. Exp. 68, e50034 (2012).

  37. 37.

    , & Biomed. Eng. Online 2, 13 (2003).

  38. 38.

    & BMC Bioinformatics 7, 123 (2006).

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Acknowledgements

We thank members of the Drenan and Lavis laboratories for helpful advice and discussion, and T. Lerner (Northwestern University, Chicago, Illinois, USA) for contributing viral reagents. This work was supported by the Howard Hughes Medical Institute (to S.B., J.J.M., and L.D.L.), the US National Institutes of Health (NIH) (grants DA035942 and DA040626 to R.M.D., MH099114 to A.C., DA037161 to H.A.L., NS054850 to D.J. Surmeier, and GM103801 and GM48677 to J.M.M.), the PhRMA Foundation (fellowship to M.C.A.), the Arnold and Mabel Beckman Foundation (Beckman Young Investigator Award to Y.K.), the Bernice E. Bumpus Foundation (Early Career Innovation Award to Y.K.), the Rita Allen Foundation (to Y.K.), the Searle Scholars Program (to Y.K.), the Alfred P. Sloan Foundation (Sloan Research Fellowship to Y.K.), NINDS (grant NINDS F32 NS103243 to N.M.B.), the JPB Foundation, and Northwestern University.

Author information

Author notes

    • Sambashiva Banala
    •  & Matthew C Arvin

    These authors contributed equally to this work.

    • Ryan M Drenan
    •  & Luke D Lavis

    These authors jointly directed this work.

Affiliations

  1. Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA.

    • Sambashiva Banala
    • , John J Macklin
    • , Henry A Lester
    •  & Luke D Lavis
  2. Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

    • Matthew C Arvin
    • , Xiao-Tao Jin
    • , Yong Wang
    • , Can Peng
    • , Guiqing Zhao
    • , Veronica J Kim
    •  & Ryan M Drenan
  3. Department of Neurobiology, Weinberg School of Arts and Sciences, Northwestern University, Evanston, Illinois, USA.

    • Nicholas M Bannon
    • , Anis Contractor
    •  & Yevgenia Kozorovitskiy
  4. Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

    • John J Marshall
    • , David L Wokosin
    •  & Anis Contractor
  5. Molecular Probes, Thermo Fisher, Eugene, Oregon, USA.

    • Kyle R Gee
  6. George E. Wahlen Veterans Affairs Medical Center and Departments of Psychiatry and Biology, University of Utah, Salt Lake City, Utah, USA.

    • J Michael McIntosh
  7. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.

    • Henry A Lester

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Contributions

R.M.D., M.C.A., H.A.L., S.B., K.R.G., and L.D.L. conceived the project. M.C.A., N.M.B., D.L.W., X.-T.J., J.J.M., Y.W., C.P., G.Z., V.J.K., J.J.M., A.C., Y.K., R.M.D., S.B., and L.D.L. planned and/or executed experiments. D.L.W., Y.K., J.M.M., and K.R.G. contributed essential reagents and expertise. R.M.D., M.C.A., S.B., and L.D.L. wrote the paper with input from all other authors. R.M.D. and L.D.L. supervised all aspects of the work.

Competing interests

K.R.G. is an employee of Thermo Fisher Scientific and has stock options. All other authors declare no competing interests.

Corresponding authors

Correspondence to Ryan M Drenan or Luke D Lavis.

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DOI

https://doi.org/10.1038/nmeth.4637