Homodimeric architecture of a CIC-type chloride ion channel (original) (raw)

Nature volume 383, pages 337–340 (1996)Cite this article

Abstract

THE recent discovery of the CIC-family of anion-conducting channel proteins1–3 has led to an appreciation of the central roles played by chloride ion channels in cellular functions, such as electrical behaviour of muscle4–7 and nerve8 and epithelial solute transport9. Little is known, however, about molecular architecture or sequence–function relationships in these membrane proteins. In the single case of C1C-0, a voltage-gated 'muscle-type' chloride channel, the functional complex is known to be a homo-oligomer of a polypeptide of _M_r ˜ 90,000, with no associated 'helper' summits10. The subunit stoichiometry of CIC-type channels is controversial, however, with either dimeric or tetrameric association suggested by different indirect experi-ments10,11. Before a coherent molecular view of this new class of ion channels can emerge, the fundamental question of subunit composition must first be settled. We have examined hybrid C1C-0 channels constructed from functionally tagged subunits, and report here that C1C-0 is a homodimer containing two chloride-conduction pores.

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References

  1. Jentsch, T. J., Steinmeyer, K. & Schwarz, G. Nature 348, 510–514 (1990).
    Article ADS CAS Google Scholar
  2. Pusch, M. & Jentsch, T. Physiol. Rev. 74, 813–825 (1994).
    Article CAS Google Scholar
  3. Jentsch, T. J., Gunther, W., Pusch, M. & Schwappach, B. J. Physiol. (Lond.) 482, 19S–25S (1995).
    Article CAS Google Scholar
  4. Palade, P. T. & Barchi, R. L. J. Gen. Physiol. 69, 879–896 (1977).
    Article CAS Google Scholar
  5. Steinmeyer, K. et al. Nature 354, 304–308 (1991).
    Article ADS CAS Google Scholar
  6. George, A. L., Carackower, M. A., Abdalla, J. A., Hudson, A. J. & Ebers, G. C. Nature Genet. 3, 305–310 (1993).
    Article CAS Google Scholar
  7. Ackerman, M. J. & Clapham, D. E. Trends Cardiovasc. Med. 3, 23–28 (1993).
    Article CAS Google Scholar
  8. Mayer, M. L. J. Physiol. (Lond.) 364, 217–239 (1985).
    Article CAS Google Scholar
  9. Lloyd, S. E. et al. Nature 379, 445–449 (1996).
    Article ADS CAS Google Scholar
  10. Middleton, R. E., Pheasant, D. J. & Miller, C. Biochemistry 33, 13189–13198 (1994).
    Article CAS Google Scholar
  11. Steinmeyer, K., Lorenz, C., Pusch, M., Koch, M. C. & Jentsch, T. J. EMBO J. 13, 737–743 (1994).
    Article CAS Google Scholar
  12. Miller, C. Phil. Trans. R. Soc. Lond. B 299, 401–411 (1982).
    Article ADS CAS Google Scholar
  13. Hanke, W. & Miller, C. J. Gen. Physiol. 82, 25–45 (1983).
    Article CAS Google Scholar
  14. Miller, C. & Richard, E. A. in Chloride Transporters (eds Leefmans, A. & Russell, J.) 383–405 (Plenum, New York, 1990).
    Google Scholar
  15. Miller, C. & White, M. M. Proc. Natl Acad. Sci. USA 81, 2772–2775 (1984).
    Article ADS CAS Google Scholar
  16. Bauer, C. K., Steinmeyer, K., Schwarz, J. R. & Jentsch, T. J. Proc. Natl Acad. Sci. USA 88, 11052–11056 (1991).
    Article ADS CAS Google Scholar
  17. Pusch, M., Ludewig, U., Rehfeldt, A. & Jentsch, T. J. Nature 373, 527–531 (1995).
    Article ADS CAS Google Scholar
  18. Cooper, E., Couturier, S. & Ballivet, M. Nature 350, 235–238 (1991).
    Article ADS CAS Google Scholar
  19. Liu, D. T., Tibbs, G. R. & Siegelbaum, S. A. Neuron 16, 983–990 (1996).
    Article CAS Google Scholar
  20. Akabas, M. H., Stauffer, D. A., Xu, M. & Karlin, A. Science 258, 307–310 (1992).
    Article ADS CAS Google Scholar
  21. Stauffer, D. A. & Karlin, A. Biochemistry 33, 6840–6849 (1994).
    Article CAS Google Scholar
  22. Hille, B. Ionic Channels of Excitable Membranes (Sinauer, Sunderland, MA, 1992).
    Google Scholar
  23. Weiss, M. S. & Schulz, G. E. J. Mol. Biol. 227, 493–509 (1992).
    Article CAS Google Scholar
  24. Cowan, S. W. et al. Nature 358, 727–733 (1992).
    Article ADS CAS Google Scholar
  25. MacKinnon, R. Neuron 14, 889–892 (1995).
    Article CAS Google Scholar
  26. Mindell, J. A., Zhan, H., Huynh, P. D., Collier, R. J. & Finkelstein, A. Proc. Natl Acad. Sci. USA 91, 5272–5276 (1994).
    Article ADS CAS Google Scholar

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts, 02254, USA
    Richard E. Middleton, Deborah J. Pheasant & Christopher Miller

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  1. Richard E. Middleton
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  2. Deborah J. Pheasant
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  3. Christopher Miller
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Middleton, R., Pheasant, D. & Miller, C. Homodimeric architecture of a CIC-type chloride ion channel.Nature 383, 337–340 (1996). https://doi.org/10.1038/383337a0

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