Skip to main content

Thank you for visiting 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:

A point mutation in a Drosophila GABA receptor confers insecticide resistance


VERTEBRATES and invertebrates both have GABA (γ-aminobutyric acid) as a major inhibitory neurotransmitter1,2. GABAA receptors in vertebrates assemble as heteromultimers to form an integral chloride ion channel3. These receptors are targets for drugs and pesticides4 and are also implicated in seizure-related diseases5,6. Picrotoxinin (PTX) and cyclodiene insecticides are GABAA receptor antagonists which competitively displace each other from the same binding site7. Insects8 and vertebrates9 showing resistance to cyclodienes also show cross-resistance to PTX. Previously, we used a field-isolated Drosophila mutant Rdl (Resistant to dieldrin)10 insensitive to PTX and cyclodienes to clone a putative GABA receptor11. Here we report the functional expression and novel pharmacology of this GABA receptor and examine the functionality of a resistance-associated point mutation (alanine to serine) within the second membrane-spanning domain, the region thought to line the chloride ion channel pore. This substitution is found globally in Drosophila populations12. This mutation not only identifies a single amino acid conferring high levels of resist-ance to the important GABA receptor antagonist PTX but also, by conferring resistance to cyclodienes, may account for over 60% of reported cases of insecticide resistance13.

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


  1. Kuffler, S. W. & Edwards, C. J. Neurophysiol. 21, 589–601 (1965).

    Article  Google Scholar 

  2. Usherwood, P. N. R. & Grundfest, H. J. Neurophysiol. 28, 497–518 (1965).

    Article  CAS  Google Scholar 

  3. Olsen, R. W. & Tobin, A. J. FASEB J. 4, 1469–1480 (1990).

    Article  CAS  Google Scholar 

  4. Eldefrawi, A. T. & Eldefrawi, M. E. FASEB J. 1, 262–271 (1987).

    Article  CAS  Google Scholar 

  5. Meldrum, B. S. Br. J. clin. Pharmacol. 27, 3S–11S (1989).

    Article  CAS  Google Scholar 

  6. Wagstaff, J. et al. Am. J. hum. Genet 49, 330–337 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Matsumura, F. & Ghiasuddin, S. M. J. environ. Sci. Hlth B18, 1–14 (1983).

    CAS  Google Scholar 

  8. Kadous, A. A., Ghiasuddin, S. M., Matsumura, F., Scott, J. G. & Tanaka, K. Pestic. Biochem. Physiol. 19, 157–166 (1983).

    Article  CAS  Google Scholar 

  9. Yarbrough, J. D., Roush, R. T., Bonner, J. C. & Wise, D. A. Experientia 42, 851–853 (1986).

    Article  CAS  Google Scholar 

  10. ffrench-Constant, R. H., Roush, R. T., Mortlock, D. & Dively, G. P. J. Ecol. Ent. 83, 1733–1737 (1990).

    Article  CAS  Google Scholar 

  11. ffrench-Constant, R. H., Mortlock, D. P., Shaffer, C. D., Maclntyre, R. J. & Roush, R. T. Proc. natn. Acad. Sci. U.S.A. 88, 7209–7213 (1991).

    Article  ADS  CAS  Google Scholar 

  12. ffrench-Constant R. H., Steichen, J., Rocheleau, T. A., Aronstin, K. & Roush, R. T. Proc. natn. Acad. Sci. U.S.A. (in the press).

  13. Georghiou, G. P. in Pesticide Resistance: Strategies and Tactics for Management 14–43 (National Academy Press, Washington DC, 1986).

    Google Scholar 

  14. Imoto, K. et al. Nature 335, 645–648 (1988).

    Article  ADS  CAS  Google Scholar 

  15. Leonard, R. J., Labarca, C. G., Charnet, P., Davidson, N. & Lester, H. A. Science 242, 1578–1581 (1988).

    Article  ADS  CAS  Google Scholar 

  16. Blair, L. A., Levitan, E. S., Marshall, J., Dionne, V. E. & Barnard, E. A. Science 242, 577–579 (1988).

    Article  ADS  CAS  Google Scholar 

  17. Lummis, S. C. Comp. Biochem. Physiol. 95, 1–8 (1990).

    Article  ADS  CAS  Google Scholar 

  18. Feigenspan, A., Wassle, H. & Bormann, J. Nature 361, 159–161 (1993).

    Article  ADS  CAS  Google Scholar 

  19. Qian, H. & Dowling, J. E. Nature 361, 162–164 (1993).

    Article  ADS  CAS  Google Scholar 

  20. Shimada, S., Cutting, G. & Uhl, G. R. Molec. Pharmac. 41, 683–687 (1992).

    CAS  Google Scholar 

  21. ffrench-Constant, R. H. & Rocheleau, T. J. Neurochem. 59, 1562–1565 (1992).

    Article  CAS  Google Scholar 

  22. Harvey, R. J. et al. EMBO J. 10, 3239–3245 (1991).

    Article  CAS  Google Scholar 

  23. Bloomquist, J. R., ffrench-Constant, R. H. & Roush, R. T. Pestic. Sci. 32, 463–469 (1991).

    Article  CAS  Google Scholar 

  24. ffrench-Constant, R. H. & Roush, R. T. Genet. Res. Camb. 57, 17–21 (1991).

    Article  CAS  Google Scholar 

  25. Pribilla, I., Takagi, T., Langosch, D., Bormann, J. & Betz, H. EMBO J. 11, 4305–4311 (1992).

    Article  CAS  Google Scholar 

  26. Roush, R. T. & McKenzie, J. A. A. Rev. Ent. 32, 361–380 (1987).

    Article  CAS  Google Scholar 

  27. Noda, M. et al. Nature 299, 793–797 (1982).

    Article  ADS  CAS  Google Scholar 

  28. Satelle, D. B. et al. in Transmitter Amino Acid Receptors, Structures, Transduction and Models for Drug Development (eds Barnard, E. A. & Costa, E.) 273–291 (Thieme Medical, New York, 1992).

    Google Scholar 

  29. Schofield, P. R. et al. Nature 328, 221–227 (1987).

    Article  ADS  CAS  Google Scholar 

  30. Pritchett, D. B. et al. Nature 338, 582–585 (1989).

    Article  ADS  CAS  Google Scholar 

  31. Shivers, B. D. et al. Neuron 3, 327–337 (1989).

    Article  CAS  Google Scholar 

  32. Cutting, G. R. et al. Proc. natn. Acad. Sci. U.S.A. 88, 2673–2677 (1991).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Reprints and permissions

About this article

Cite this article

ffrench-Constant, R., Rocheleau, T., Steichen, J. et al. A point mutation in a Drosophila GABA receptor confers insecticide resistance. Nature 363, 449–451 (1993).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


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.


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