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An unsaturated aliphatic alcohol as a natural ligand for a mouse odorant receptor

Nature Chemical Biology volume 9, pages 160–162 (2013)Cite this article

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Abstract

We report the identification of a physiological receptor-volatile pair in the mouse olfactory system. By activity-guided fractionation of exocrine gland extracts and subsequent chemical analysis, (Z)-5-tetradecen-1-ol was identified as a natural ligand for a mouse odorant receptor. (Z)-5-tetradecen-1-ol is excreted into male mouse urine under androgen control and enhances urine attractiveness to female mice. This report is to our knowledge the first to describe natural product–based deorphanization of an odorant receptor.

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Figure 1: Responses of Olfr288-expressing oocytes to exocrine gland extracts.
Figure 2: Purification and identification of ligand for Olfr288 in PPG extract.
Figure 3: Z5-14:OH is a PPG-derived male urinary volatile that enhances urine attractiveness to female mice.

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References

  1. Nei, M., Niimura, Y. & Nozawa, M. Nat. Rev. Genet. 9, 951–963 (2008).

    Article  CAS  Google Scholar 

  2. Touhara, K. & Vosshall, L.B. Annu. Rev. Physiol. 71, 307–332 (2009).

    Article  CAS  Google Scholar 

  3. Saito, H., Chi, Q., Zhuang, H., Matsunami, H. & Mainland, J.D. Sci. Signal. 2, ra9 (2009).

    Article  Google Scholar 

  4. Civelli, O. FEBS Lett. 430, 55–58 (1998).

    Article  CAS  Google Scholar 

  5. Touhara, K. Neurochem. Int. 51, 132–139 (2007).

    Article  CAS  Google Scholar 

  6. Uezono, Y. et al. Receptors Channels 1, 233–241 (1993).

    CAS  PubMed  Google Scholar 

  7. Katada, S., Nakagawa, T., Kataoka, H. & Touhara, K. Biochem. Biophys. Res. Commun. 305, 964–969 (2003).

    Article  CAS  Google Scholar 

  8. Abaffy, T., Matsunami, H. & Luetje, C.W. J. Neurochem. 97, 1506–1518 (2006).

    Article  CAS  Google Scholar 

  9. Saito, H., Kubota, M., Roberts, R.W., Chi, Q. & Matsunami, H. Cell 119, 679–691 (2004).

    Article  CAS  Google Scholar 

  10. Zhuang, H. & Matsunami, H. J. Biol. Chem. 282, 15284–15293 (2007).

    Article  CAS  Google Scholar 

  11. Von Dannecker, L.E., Mercadante, A.F. & Malnic, B. Proc. Natl. Acad. Sci. USA 103, 9310–9314 (2006).

    Article  CAS  Google Scholar 

  12. Yoshikawa, K. & Touhara, K. Chem. Senses 34, 15–23 (2009).

    Article  CAS  Google Scholar 

  13. Oka, Y. et al. Neuron 52, 857–869 (2006).

    Article  CAS  Google Scholar 

  14. Bozza, T., Feinstein, P., Zheng, C. & Mombaerts, P. J. Neurosci. 22, 3033–3043 (2002).

    Article  CAS  Google Scholar 

  15. Touhara, K. et al. Proc. Natl. Acad. Sci. USA 96, 4040–4045 (1999).

    Article  CAS  Google Scholar 

  16. Katada, S., Hirokawa, T., Oka, Y., Suwa, M. & Touhara, K. J. Neurosci. 25, 1806–1815 (2005).

    Article  CAS  Google Scholar 

  17. Tan, J., Savigner, A., Ma, M. & Luo, M. Neuron 65, 912–926 (2010).

    Article  CAS  Google Scholar 

  18. Buser, H.R., Arn, H., Guerin, P. & Rauscher, S. Anal. Chem. 55, 818–822 (1983).

    Article  CAS  Google Scholar 

  19. Bartelt, J.R., Jones, L.R. & Krick, P.T. J. Chem. Ecol. 9, 1343–1352 (1983).

    Article  CAS  Google Scholar 

  20. Evans, C.M. & Brain, F.P. Physiol. Behav. 21, 19–23 (1978).

    Article  CAS  Google Scholar 

  21. Mugford, R.A. & Nowell, N.W. Horm. Behav. 3, 39–46 (1972).

    Article  CAS  Google Scholar 

  22. Jemiolo, B., Alberts, J., Sochinski-Wiggins, S., Harvey, S. & Novotny, M. Anim. Behav. 33, 1114–1118 (1985).

    Article  Google Scholar 

  23. Lin, D.Y., Zhang, S.Z., Block, E. & Katz, L.C. Nature 434, 470–477 (2005).

    Article  CAS  Google Scholar 

  24. Horiike, M., Tanouchi, M. & Hirano, C. Agric. Biol. Chem. 44, 257–261 (1980).

    CAS  Google Scholar 

  25. Cork, A., Murlis, J. & Megenasa, T. J. Chem. Ecol. 15, 1349–1364 (1989).

    Article  CAS  Google Scholar 

  26. Krautwurst, D., Yau, K.W. & Reed, R.R. Cell 95, 917–926 (1998).

    Article  CAS  Google Scholar 

  27. Fukuda, N. et al. Eur. J. Neurosci. 27, 2665–2675 (2008).

    Article  Google Scholar 

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Acknowledgements

This work was supported in part by a Grant-in-Aid for Scientific Research (S) from the Ministry of Education, Culture, Sports, Science and Technology Japan (grant 24227003), a Grant-in-Aid for Scientific Research on Priority Areas from the Japan Society for the Promotion of Science (JSPS) (grant 18077001) and a research grant from the Astellas Foundation for Research on Metabolic Disorders to K.T. K.Y. was supported by a Grant-in-Aid for JSPS fellows. We thank T. Ando for Z8-14:OH (Tokyo University of Agriculture and Technology), and T. Kikusui and T. Hattori for advice on behavioral experiments.

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Authors and Affiliations

  1. Department of Applied Biological Chemistry, The University of Tokyo, Tokyo, Japan

    Keiichi Yoshikawa, Hiroaki Nakagawa, Naoki Mori, Hidenori Watanabe & Kazushige Touhara

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  1. Keiichi Yoshikawa
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  2. Hiroaki Nakagawa
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  3. Naoki Mori
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  4. Hidenori Watanabe
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  5. Kazushige Touhara
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Contributions

K.Y. performed experiments; H.N. identified δ-undecalactone as a synthetic ligand for Olfr288; N.M. generated the reagents; K.Y and K.T. designed the research, analyzed data and wrote the manuscript; H.W. and K.T. supervised the work.

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Correspondence to Kazushige Touhara.

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The authors declare no competing financial interests.

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Yoshikawa, K., Nakagawa, H., Mori, N. et al. An unsaturated aliphatic alcohol as a natural ligand for a mouse odorant receptor. Nat Chem Biol 9, 160–162 (2013). https://doi.org/10.1038/nchembio.1164

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