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Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic

Abstract

Introduction by site-directed mutagenesis of three amino acids from the Mil segment of glycine or & GAMMA;-aminobutyric acid (GABAA) receptors into the Mil segment of α7 nicotinic receptor was sufficient to convert a cation-selective channel into an an ion-selective channel gated by acetylcholine. A critical mutation was the insertion of an uncharged residue at the amino-terminal end of Mil, stressing the importance of protein geometrical constraints on ion selectivity.

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References

  1. Betz, H. Neuron 5, 383–392 (1990).

    Article  CAS  Google Scholar 

  2. Galzi, J. L., Revah, F., Bessis, A. & Changeux, J. P. A. Rev. Pharmac. Tox. 31, 37–72 (1991).

    Article  CAS  Google Scholar 

  3. Seeburg, P. H. et al. Cold Spring Harb. Symp. Quant. Biol. 55, 29–40 (1991).

    Article  Google Scholar 

  4. Maricq, A. V., Peterson, A. S., Brake, A. J., Myers, R. M. & Julius, D. Science 254, 432–437 (1991).

    Article  ADS  CAS  Google Scholar 

  5. Giraudat, J., Dennis, M., Heidmann, T., Chang, J. Y. & Changeux, J. P. Proc. natn. Acad. Sci. U.S.A. 83, 2719–2723 (1986).

    Article  ADS  CAS  Google Scholar 

  6. Hucho, F., Oberthür, W. & Lottspeich, F. FEBS Lett. 205, 137–142 (1986).

    Article  CAS  Google Scholar 

  7. Revah, F. et al. Proc. natn. Acad. Sci. U.S.A. 87, 4675–4679 (1990).

    Article  ADS  CAS  Google Scholar 

  8. Imoto, K. et al. Nature 324, 670–674 (1986).

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  10. Heidmann, T. & Changeux, J. P. Eur. J. Biochem. 94, 281–296 (1979).

    Article  CAS  Google Scholar 

  11. Neubig, R., Boyd, N. & Cohen, J. B. Biochemistry 21, 3460–3467 (1982).

    Article  CAS  Google Scholar 

  12. Katz, B. & Thesleff, S. J. Physiol., Lond. 138, 63–80 (1957).

    Article  CAS  Google Scholar 

  13. Sakmann, B., Patlak, J. & Neher, E. Nature 286, 71–73 (1980).

    Article  ADS  CAS  Google Scholar 

  14. Couturier, S. et al. Neuron 5, 847–856 (1990).

    Article  CAS  Google Scholar 

  15. Schoepfer, R., Conroy, W. G., Whithing, P., Gore, M. & Lindstrom, J. Neuron 5, 35–48 (1990).

    Article  CAS  Google Scholar 

  16. Revah, F. et al. Nature 353, 846–849 (1991).

    Article  ADS  CAS  Google Scholar 

  17. Bertrand, D. et al. Proc. natn. Acad. Sci. U.S.A. 89, 1261–1265 (1992).

    Article  ADS  CAS  Google Scholar 

  18. Bormann, J., Hammill, O. P. & Sakmann, B. J. Physiol., Lond. 385, 243–286 (1987).

    Article  CAS  Google Scholar 

  19. Charnet, P. et al. Neuron 4, 87–95 (1990).

    Article  CAS  Google Scholar 

  20. Imoto, K. et al. FEBS Lett. 289, 193–200 (1991)

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  22. Giraudat, J. et al. Biochemistry 26, 2410–2418 (1987).

    Article  CAS  Google Scholar 

  23. Langosch, D., Hartung, K., Grell, E., Bamberg, E. & Betz, H. Biochim. biophys. Acta 1063, 36–44 (1991).

    Article  CAS  Google Scholar 

  24. Grenningloh, G. et al. Nature 328, 215–220 (1987).

    Article  ADS  CAS  Google Scholar 

  25. Hollmann, M., Hartley, M. & Heinemann, S. Science 252, 851–853 (1991).

    Article  ADS  CAS  Google Scholar 

  26. Verdoorn, T. A., Burnashev, N., Monyer, H., Seeburg, P. H. & Sakmann, B. Science 252, 1715–1718 (1991).

    Article  ADS  CAS  Google Scholar 

  27. Curutchet, P. et al. Biochem. biophys. Res. Commun. 182, 1089–1093 (1992).

    Article  CAS  Google Scholar 

  28. Mulle, C., Choquet, D., Korn, H. & Changeux, J. P. Neuron 8, 135–143 (1992).

    Article  CAS  Google Scholar 

  29. Vernino, S., Amador, M., Luetje, C. W., Patrick, J. & Dani, J. A. Neuron 8, 127–134 (1992).

    Article  CAS  Google Scholar 

  30. Vernino, S., Amador, M. & Dani, J. A. J. Cell Biochem. 16E (suppl.) 217 (1992).

    Google Scholar 

  31. Miledi, R. Proc. R. Soc. B215, 491–497 (1982).

    ADS  CAS  Google Scholar 

  32. Miledi, R. & Parker, I. J. Physiol., Lond. 357, 173–183 (1984).

    Article  CAS  Google Scholar 

  33. Tsien, R. Y. Biochemistry 19, 2396–2404 (1980).

    Article  CAS  Google Scholar 

  34. Pullman, A. Chem. Rev. 91, 793–812 (1991).

    Article  CAS  Google Scholar 

  35. Unwin, N. Neuron 3, 665–676 (1989).

    Article  CAS  Google Scholar 

  36. Bertrand, D., Bertrand, S. & Ballivet, M. Neurosci. Lett. (in the press).

  37. Konno, T. et al. Proc. R. Soc. B244, 69–79 (1991).

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  39. Tauc, L. & Gershenfeld, H. M. J. Neurophysiol. 25, 236–262 (1962).

    Article  CAS  Google Scholar 

  40. Kehoe, J. J. Physiol., Lond. 225, 85–114 (1972).

    Article  CAS  Google Scholar 

  41. Ascher, P. & Ekulkar, S. in Single–channel Recording (eds Sakmann, B. & Neher, E.) 401–406 (Plenum, New York, London, 1983).

    Book  Google Scholar 

  42. Arena, J. P., Liu, K. K., Paress, P. S. & Cully, D. F. J. Cell. Biochem. 16E (suppl.) 226 (1992).

    Google Scholar 

  43. Franciolini, F. & Petris, A. Biochim. biophys. Acta 1031, 247–259 (1990).

    Article  CAS  Google Scholar 

  44. Lo, D. C., Pinkham, J. L. & Stevens C. F. Neuron 6, 31–40 (1991).

    Article  CAS  Google Scholar 

  45. Unwin, N., Toyoshima, C. & Kubalek, E. J. Cell Biol. 107, 1123–1138 (1988).

    Article  CAS  Google Scholar 

  46. Galzi, J. L. et al. Proc. natn. Acad. Sci. U.S.A. 88, 5051–5055 (1991).

    Article  ADS  CAS  Google Scholar 

  47. Karlin, A. The Harvey Lectures, Series 85 71–107 (Wiley-Liss, New York, 1991).

    Google Scholar 

  48. Newland, C. F., Colquhoun, D. & Cull-Candy, S. J. Physiol., Lond. 432, 203–233 (1991).

    Article  CAS  Google Scholar 

  49. Grenningloh, G. et al. Neuron 4, 963–970 (1990).

    Article  CAS  Google Scholar 

  50. Hodgkin, A. L. Biol. Rev. 26, 339–409 (1951).

    Article  CAS  Google Scholar 

  51. Bertrand, D., Cooper, E., Valera, S., Rungger, D. & Ballivet, M. Methods in Neuroscience Vol. 4 (ed. Conn. P. M.) 174–193 (Academic, San Diego, 1991).

    Article  Google Scholar 

  52. Devillers-Thiéry, A., Galzi, J. L., Bertrand, S., Changeux, J. P. & Bertrand, D. Neuroreport (in the press).

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Galzi, JL., Devillers-Thiery, A., Hussy, N. et al. Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic. Nature 359, 500–505 (1992). https://doi.org/10.1038/359500a0

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