Chemical structure and biological activity of the Caenorhabditis elegans dauer-inducing pheromone (original) (raw)

Nature volume 433, pages 541–545 (2005)Cite this article

Abstract

Pheromones are cell type-specific signals used for communication between individuals of the same species. When faced with overcrowding or starvation, Caenorhabditis elegans secrete the pheromone daumone, which facilitates communication between individuals for adaptation to adverse environmental stimuli1,2,3,4. Daumone signals C. elegans to enter the dauer stage, an enduring and non-ageing stage of the nematode life cycle with distinctive adaptive features and extended life. Because daumone is a key regulator of chemosensory processes in development and ageing5,6, the chemical identification of daumone is important for elucidating features of the daumone-mediated signalling pathway. Here we report the isolation of natural daumone from C. elegans by large-scale purification, as well as the total chemical synthesis of daumone. We present the stereospecific chemical structure of purified daumone, a fatty acid derivative. We demonstrate that both natural and chemically synthesized daumones equally induce dauer larva formation in C. elegans (N2 strain) and certain dauer mutants, and also result in competition between food and daumone. These results should help to elucidate the daumone-mediated signalling pathway, which might in turn influence ageing and obesity research and the development of antinematodal drugs.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Cassada, R. C. & Russell, R. L. The dauer larva, a post-embryonic developmental variant of the nematode Caenorhabditis elegans . Dev. Biol. 46, 326–342 (1975)
    Article CAS PubMed Google Scholar
  2. Golden, J. W. & Riddle, D. L. A pheromone influences larval development in the nematode Caenorhabditis elegans . Science 218, 578–580 (1982)
    Article ADS CAS PubMed Google Scholar
  3. Golden, J. W. & Riddle, D. L. The Caenorhabditis elegans dauer larva: developmental effects of pheromone, food, and temperature. Dev. Biol. 102, 368–378 (1984)
    Article CAS PubMed Google Scholar
  4. Golden, J. W. & Riddle, D. L. A Caenorhabditis elegans dauer-inducing pheromone and an antagonistic component of the food supply. J. Chem. Ecol. 10, 1265–1280 (1984)
    Article CAS PubMed Google Scholar
  5. Bargmann, C. I. & Horvitz, H. R. Control of larval development by chemosensory neurons in Caenorhabditis elegans . Science 251, 1243–1246 (1991)
    Article ADS CAS PubMed Google Scholar
  6. Schackwitz, W. S., Inoue, T. & Thomas, J. H. Chemosensory neurons function in parallel to mediate a pheromone response in C. elegans . Neuron 17, 719–728 (1996)
    Article CAS PubMed Google Scholar
  7. Thomas, J. H., Birnby, D. A. & Vowels, J. J. Evidence for parallel processing of sensory information controlling dauer formation in Caenorhabditis elegans . Genetics 134, 1105–1117 (1993)
    CAS PubMed PubMed Central Google Scholar
  8. Patterson, G. I., Koweek, A., Wong, A., Liu, Y. & Ruvkun, G. The DAF-3 Smad protein antagonizes TGF-beta-related receptor signaling in the Caenorhabditis elegans dauer pathway. Genes Dev. 11, 2679–2690 (1997)
    Article CAS PubMed PubMed Central Google Scholar
  9. Apfeld, J. & Kenyon, C. Regulation of lifespan by sensory perception in Caenorhabditis elegans . Nature 402, 804–809 (1999)
    Article ADS CAS PubMed Google Scholar
  10. Perkins, L. A., Hedgecock, E. M., Thomson, J. N. & Culotii, J. G. Mutant sensory cilia in the nematode Caenorhabditis elegans . Dev. Biol. 117, 456–487 (1986)
    Article CAS PubMed Google Scholar
  11. Antebi, A., Culotti, J. G. & Hedgecock, E. M. daf-12 regulates developmental age and the dauer alternative in Caenorhabditis elegans . Development 125, 1191–1205 (1998)
    CAS PubMed Google Scholar
  12. Bird, D. M. & Opperman, C. H. Caenorhabditis elegans: A genetic guide to parasitic nematode biology. J. Nematol. 30, 299–308 (1998)
    CAS PubMed PubMed Central Google Scholar
  13. Viney, M. F. & Franks, N. R. Is dauer pheromone of Caenorhabditis elegans really a pheromone? Naturwissenschaften 91, 123–124 (2004)
    Article ADS CAS PubMed Google Scholar
  14. Regnier, F. E. & Law, J. H. Insect pheromone. J. Lipid Res. 9, 541–551 (1968)
    CAS PubMed Google Scholar
  15. Koga, M., Take-uchi, M., Tameishi, T. & Ohshima, Y. Control of DAF-7 TGF-(alpha) expression and neuronal process development by a receptor tyrosine kinase KIN-8 in Caenorhabditis elegans . Development 126, 5387–5398 (1999)
    CAS PubMed Google Scholar
  16. Brenner, S. The genetics of Caenorhabditis elegans . Genetics 77, 71–94 (1974)
    CAS PubMed PubMed Central Google Scholar
  17. Choi, B. K., Chitwood, D. J. & Paik, Y.-K. Proteomic changes during disturbance of cholesterol metabolism by azacoprostane treatment in Caenorhabditis elegans . Mol. Cell. Proteomics 2, 1086–1095 (2003)
    Article CAS PubMed Google Scholar
  18. Vowels, J. J. & Thomas, J. H. Multiple chemosensory defects in daf-11 and daf-21 mutants of Caenorhabditis elegans . Genetics 138, 303–316 (1994)
    CAS PubMed PubMed Central Google Scholar
  19. Kimura, K. D., Tissenbaum, H. A., Liu, Y. & Ruvkun, G. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans . Science 277, 942–946 (1997)
    Article CAS PubMed Google Scholar
  20. Rance, M. et al. Improved spectral resolution in cosy 1H NMR spectra of proteins via double quantum filtering. Biochem. Biophys. Res. Commun. 117, 479–485 (1983)
    Article CAS PubMed Google Scholar
  21. Bax, A. & Subramanian, S. Sensitivity-enhanced two-dimensional heteronuclear shift correlation NMR spectroscopy. J. Magn. Reson. 67, 565–570 (1986)
    ADS CAS Google Scholar
  22. Bax, A. & Davis, D. G. Practical aspects of two-dimensional transverse NOE spectroscopy. J. Magn. Reson. 63, 207–213 (1985)
    ADS CAS Google Scholar
  23. Bax, A., Griffey, R. H. & Hawkins, B. L. Correlation of proton and nitrogen-15 chemical shifts by multiple quantum NMR. J. Magn. Reson. 55, 301–315 (1983)
    ADS CAS Google Scholar
  24. Bax, A. & Summers, M. F. 1H and 13C assignments from sensitivity enhanced detection of heteronuclear multiple-bond connectivity by two-dimensional multiple quantum NMR. J. Am. Chem. Soc. 108, 2093–2094 (1986)
    Article CAS Google Scholar
  25. Schleucher, J. et al. A general enhancement scheme in heteronuclear multidimensional NMR employing pulsed field gradients. J. Biomol. NMR 4, 301–306 (1994)
    Article CAS PubMed Google Scholar

Download references

Acknowledgements

This study was supported by a grant to Y.K.P. from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea. We thank J.-M. Kim at KDR Biotech Co. for his support on this project, D.J. Chitwood at the USDA-ARS Nematology Lab for his critical reading and suggestions, R. Moyer at King College (USA) for editorial assistance, J. Lee at Seoul National University for discussions and the Caenorhabditis Genetics Center for kind provision of the C. elegans strains used in this study. Technical support from the LG Chem Research Center (Taejon, Korea) was appreciated.

Author information

Authors and Affiliations

  1. Department of Biochemistry and Yonsei Proteome Research Center,
    Pan-Young Jeong, Eunmi Hong, Weontae Lee & Young-Ki Paik
  2. Department of Chemistry,
    Mankil Jung, Heekyeong Kim & Moonsoo Park
  3. Bioproducts Research Center, Yonsei University, 120-749, Seoul, Korea
    Kun Kim
  4. Korea Research Institute of Standards and Science, 305-600, Taejon, Korea
    Yong-Hyeon Yim
  5. Korea Basic Science Institute, 305-333, Taejeon, Korea
    Young Hwan Kim

Authors

  1. Pan-Young Jeong
    You can also search for this author inPubMed Google Scholar
  2. Mankil Jung
    You can also search for this author inPubMed Google Scholar
  3. Yong-Hyeon Yim
    You can also search for this author inPubMed Google Scholar
  4. Heekyeong Kim
    You can also search for this author inPubMed Google Scholar
  5. Moonsoo Park
    You can also search for this author inPubMed Google Scholar
  6. Eunmi Hong
    You can also search for this author inPubMed Google Scholar
  7. Weontae Lee
    You can also search for this author inPubMed Google Scholar
  8. Young Hwan Kim
    You can also search for this author inPubMed Google Scholar
  9. Kun Kim
    You can also search for this author inPubMed Google Scholar
  10. Young-Ki Paik
    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toYoung-Ki Paik.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

Rights and permissions

About this article

Cite this article

Jeong, PY., Jung, M., Yim, YH. et al. Chemical structure and biological activity of the Caenorhabditis elegans dauer-inducing pheromone.Nature 433, 541–545 (2005). https://doi.org/10.1038/nature03201

Download citation

This article is cited by

Editorial Summary

Dauer consequences

The dauer form in the nematode C. elegans is a non-ageing stage of the life cycle conducive to survival in adverse conditions such as food shortage. The properties of the natural dauer-inducing pheromone (‘daumone’) that regulates ageing and development in C. elegans have been studied for many years, but its precise biochemical identity remained unknown. Daumone has now been purified and fully characterized and, as predicted, it is a fatty acid derivative. Natural and chemically synthesized daumones equally induce dauer larva formation. This work could lead to novel antinematodal drugs and is relevant to research into ageing and obesity.