Genes required for GABA function in Caenorhabditis elegans (original) (raw)

Nature volume 364, pages 334–337 (1993)Cite this article

Abstract

γ-AMINOBITYRIC acid (GABA) neurotransmission is widespread in vertebrate and invertebrate nervous systems1. Here we use a genetic approach to identify molecules specific to GABA function. On the basis of the known in vivo roles of GABAergic neurons in controlling behaviour of the nematode _Caenorhabditis elegans_2, we identified mutants defective in GABA-mediated behaviours. Five genes are necessary either for GABAergic neuronal differentiation or for pre- or postsynaptic GABAergic function. The gene unc-30 is required for the differentiation of a specific type of GABAergic neuron, the type-D inhibitory motor neuron. The gene unc-25 is necessary for GABA expression and probably encodes the GABA biosynthetic enzyme glutamic acid decarboxylase. The genes unc-46 and unc-47 seem to be required for normal GABA release. Finally, the gene unc-49 is apparently necessary postsynaptically for the inhibitory effect of GABA on the body muscles and might encode a protein needed for the function of a GABAA-like receptor. Some of these genes are likely to encode previously unidentified proteins required for GABA function.

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References

  1. Cooper, J. R., Bloom, F. E. & Roth, R. H. The Biochemical Basis of Neuropharmacology 1, 133–166 (Oxford University Press, New York, 1991).
    Google Scholar
  2. McIntire, S. L., Jorgensen, E., Kaplan, J. & Horvitz, H. R. Nature 364, 337–341 (1993).
    Article ADS CAS PubMed Google Scholar
  3. Brenner, S. Genetics 77, 71–94 (1974).
    CAS PubMed PubMed Central Google Scholar
  4. Hodgkin, J. Genetics 103, 43–64 (1983).
    CAS PubMed PubMed Central Google Scholar
  5. Kass, I. S., Stretton, A. O. W. & Wang, C. C. Molec. Biochem. Parasit. 13, 213–225 (1984).
    Article CAS Google Scholar
  6. White, J. G., Southgate, E., Thomson, J. N. & Brenner, S. Phil. Trans. R. Soc. Lond. B 314, 1–340 (1986).
    Article ADS CAS Google Scholar
  7. Avery, L. A. & Horvitz, H. R. Neuron 3, 473–485 (1989).
    Article CAS PubMed Google Scholar
  8. Hedgecock, E. GABA Metabolism in Caenorhabditis elegans (Univ. California Press, Santa Cruz, 1976).
    Google Scholar
  9. Erlander, M. G. & Tobin, A. J. Neurochem. Res. 16, 215–226 (1991).
    Article CAS PubMed Google Scholar
  10. Burger, P. M. et al. Neuron 7, 287–293 (1991).
    Article CAS PubMed Google Scholar
  11. Ffrench, C. R. H., Shaffer, C. D., MacIntyre, R. J. & Roush, R. T. Proc. natn. Acad. Sci. U.S.A. 88, 7209–7213 (1991).
    Article ADS Google Scholar
  12. Meir, E., Hertz, L. & Schousboe, A. Neurochem. Int. 19, 1–15 (1991).
    Article Google Scholar
  13. Thomas, J. H. Genetics 124, 855–872 (1990).
    CAS PubMed PubMed Central Google Scholar
  14. Sulston, J. E. & White, J. G. Devl Biol. 78, 577–597 (1980).
    Article CAS Google Scholar
  15. Guastella, J. & Stretton, A. O. W. J. comp. Neurol. 307, 598–608 (1991).
    Article CAS PubMed Google Scholar
  16. Wood, W. B. et al. The Nernatode Caenorhabditis elegans (Cold Spring Harbor Laboratory Press, NY, 1988).
    Google Scholar
  17. McIntire, S. L., Garriga, G., White, J., Jacobson, D. & Horvitz, H. R. Neuron 8, 307–322 (1992).
    Article CAS PubMed Google Scholar
  18. Ferguson, E. L. & Horvitz, H. R. Genetics 110, 17–72 (1985).
    CAS PubMed PubMed Central Google Scholar

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Author notes

  1. Steven L. Mclntire
    Present address: Department of Neurology, University of California, Box 0114, M-794, San Francisco, California, 94143-0114, USA
  2. Steven L. Mclntire: Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA

Authors and Affiliations

  1. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Room 56-629, 77 Massachusetts Avenue, Cambridge, Massachusetts, 02139, USA
    Steven L. Mclntire, Erik Jorgensen & H. Robert Horvitz

Authors

  1. Steven L. Mclntire
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  2. Erik Jorgensen
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  3. H. Robert Horvitz
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Mclntire, S., Jorgensen, E. & Horvitz, H. Genes required for GABA function in Caenorhabditis elegans.Nature 364, 334–337 (1993). https://doi.org/10.1038/364334a0

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