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.

  • Letter
  • Published:

Molecular cloning and expression of brain-derived neurotrophic factor

Abstract

DURING the development of the vertebrate nervous system, many neurons depend for survival on interactions with their target cells1. Specific proteins are thought to be released by the target cells and to play an essential role in these interactions. So far, only one such protein, nerve growth factor, has been fully characterized. This has been possible because of the extraordinarily (and unex-plained) large quantities of this protein in some adult tissues that are of no relevance to the developing nervous system2. Whereas the dependency of many neurons on their target cells for normal development, and the restricted neuronal specificity of nerve growth factor have long suggested the existence of other such proteins, their low abundance has rendered their characterization difficult. Here we report the full primary structure of brain-derived neurotrophic factor. This very rare protein is known to promote the survival of neuronal populations that are all located either in the central nervous system or directly connected with it3. The messenger RNA for brain-derived neurotrophic factor was found predominantly in the central nervous system, and the sequence of the protein indicates that it is structurally related to nerve growth factor. These results establish that these two neurotrophic factors are related both functionally and structurally.

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

Access options

Buy this article

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

Similar content being viewed by others

References

  1. Purves, D. in Body and Brain. A Tropic Theory of Neural Connections (Harvard University Press, Cambridge 1988).

    Google Scholar 

  2. Cohen, S. Proc. natn. Acad. Sci. U.S.A. 46, 302–311 (1960).

    Article  ADS  CAS  Google Scholar 

  3. Barde, Y.-A. Neuron 2, 1525–1534 (1989).

    Article  CAS  PubMed  Google Scholar 

  4. Barde, Y.-A., Edgar, D. & Thoenen, H. EMBO J. 1, 549–553 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hofer, M. M. & Barde, Y.-A. Nature 331, 261–262 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  6. Saiki, R. K. et al. Science 230, 1350–1354 (1985).

    Article  ADS  CAS  PubMed  Google Scholar 

  7. Johnson, J. E., Barde, Y.-A., Schwab, M. & Thoenen, H. J. Neuroscience 6, 3031–3038 (1986).

    Article  CAS  Google Scholar 

  8. Campos-Ortega, J. A. Brain Res. 19, 306–312 (1970).

    Article  CAS  PubMed  Google Scholar 

  9. Lindsay, R. M., Thoenen, H. & Barde, Y.-A. Devl Biol. 112, 319–328 (1985).

    Article  CAS  Google Scholar 

  10. Edwards, R. H. et al. Molec. cell. Biol. 8, 2456–2464 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Schwarz, M. A., Fisher, D., Bradshaw, R. A. & Jackson, P. J. J. Neurochem. 52, 1203–1209 (1989).

    Article  CAS  PubMed  Google Scholar 

  12. Davies, A. M., Thoenen, H. & Barde, Y.-A. J. Neurosci. 6, 1897–1904 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Heumann, R., Korsching, S., Scott, J. & Thoenen, H. EMBO J. 3, 3183–3189 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Shelton, D. L. & Reichardt, L. F. Proc. natn. Acad. Sci. U.S.A. 81, 7951–7955 (1984).

    Article  ADS  CAS  Google Scholar 

  15. Swank, R. T. & Munkres, K. D. Analyt. Biochem. 39, 462–477 (1971).

    Article  CAS  PubMed  Google Scholar 

  16. Hewick, R. M., Hunkapiller M. W., Hood, L. E. & Dreyer, W. J. J. biol. Chem. 256, 7990–7997 (1981).

    CAS  PubMed  Google Scholar 

  17. Hunkapiller, M. W. et al. Meth. Enzym. 91, 227–236 (1983).

    Article  CAS  PubMed  Google Scholar 

  18. Lottspeich, F. J. Chromat 326, 321–327 (1985).

    Article  CAS  Google Scholar 

  19. Korsching, S., & Thoenen, H. Proc. natn. Acad. Sci. U.S.A. 80, 3513–3516 (1983).

    Article  ADS  CAS  Google Scholar 

  20. Andersson, S. et al. J. biol. Chem. 264, 8222–8229 (1989).

    CAS  PubMed  Google Scholar 

  21. Chen, C. & Okayama, H. Molec. cell. Biol. 7, 2745–2752 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Herrmann, G., & Frischauf, A.-M. Meth. Enzym. 152, 180–183 (1987).

    Article  CAS  PubMed  Google Scholar 

  23. Innis, M. A., Myambo, K. B., Gelfand, D. H. & Brow, M. A. D. Proc. natn. Acad. Sci. U.S.A. 85, 9436–9440 (1988).

    Article  ADS  CAS  Google Scholar 

  24. Sanger, F., Nickel, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 72, 3918–3921 (1979).

    Google Scholar 

  25. Frohman, M. A., Dush, M. K. & Martin, G. R. Proc. natn. Acad. Sci. U.S.A. 85, 8998–9002 (1988).

    Article  ADS  CAS  Google Scholar 

  26. Feinberg, A. P. & Vogelstein, B. Analyt. Biochem. 137, 266–267 (1979).

    Google Scholar 

  27. Scott, J. et al. Nature 302, 538–540 (1983).

    Article  ADS  CAS  PubMed  Google Scholar 

  28. Okayama, H. et al. Meth. Enzym. 154, 3–28 (1987).

    Article  CAS  PubMed  Google Scholar 

  29. Lehrach, R., Diamond, D., Worney, J. & Boedtker, H. Biochemistry 16, 4743–4751 (1977).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leibrock, J., Lottspeich, F., Hohn, A. et al. Molecular cloning and expression of brain-derived neurotrophic factor. Nature 341, 149–152 (1989). https://doi.org/10.1038/341149a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/341149a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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