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Cleavage of syntaxin prevents G-protein regulation of presynaptic calcium channels

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Abstract

Neurotransmitter release into the synapse is stimulated by calcium influx through ion channels that are closely associated with the transmitter release sites1,2. This link may involve the membrane protein syntaxin, which is known to be associated with the release sites and to bind to the calcium channels3,4. There is evidence that presynaptic calcium channels are downregulated by second messenger pathways involving G proteins5,6. Here we use the patch-clamp technique to test whether calcium current is regulated by G proteins in a vertebrate presynaptic nerve terminal7, and whether this regulation is affected by the linkage to syntaxin. The calcium current in the nerve terminal showed typical G-protein-mediated changes in amplitude and activation kinetics which were reversed by a preceding depolarization. These effects of the G protein were virtually eliminated if syntaxin was first cleaved with botulinum toxin C1. Our findings indicate that this sensitivity of the current to modulation by G proteins requires the association of the presynaptic calcium channel with elements of the transmitter release site, which may ensure that channels tethered at release sites2,8 are preferentially regulated by the G-protein second messenger pathway.

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References

  1. Llinas, R. R., Steinberg, I. Z. & Walton, K. Biophys. J. 33, 323–351 (1981).

    Article  CAS  Google Scholar 

  2. Stanley, E. F. Neuron 11, 1007–1011 (1993).

    Article  CAS  Google Scholar 

  3. Yoshida, A. et al. J. Biol. Chem. 267, 24925–24928 (1992).

    CAS  PubMed  Google Scholar 

  4. Sheng, Z.-H., Rettig, J., Takahashi, M. & Catterall, W. A. Neuron 13, 1303–1313 (1994).

    Article  CAS  Google Scholar 

  5. Hille, B. Trends Neurosci. 17, 531–535 (1994).

    Article  CAS  Google Scholar 

  6. Dolphin, A. C. Exp. Physiol. 80, 1–36 (1995).

    Article  CAS  Google Scholar 

  7. Stanley, E. F. & Goping, G. J. Neurosci. 11, 985–993 (1991).

    Article  CAS  Google Scholar 

  8. O'Connor, V. M., Shamotienko, O., Grishin, E. & Betz, H. FEBS Lett. 326, 255–260 (1993).

    Article  CAS  Google Scholar 

  9. Stanley, E. F. Brain Res. 505, 341–345 (1989).

    Article  CAS  Google Scholar 

  10. Yawo, H. & Momiyama, A. J. Physiol. (Lond.) 460, 153–172 (1993).

    Article  CAS  Google Scholar 

  11. Stanley, E. F. Neuron 7, 585–591 (1991).

    Article  CAS  Google Scholar 

  12. Scott, R. H. & Dolphin, A. C. Neurosci. Lett. 69, 59–64 (1986).

    Article  CAS  Google Scholar 

  13. Marchetti, C. & Robello, M. Biophys. J. 56, 1267–1272 (1989).

    Article  CAS  Google Scholar 

  14. Grassi, F. & Lux, H.-D. Neurosci. Lett. 105, 113–119 (1989).

    Article  CAS  Google Scholar 

  15. Bean, B. P. Nature 340, 153–156 (1989).

    Article  ADS  CAS  Google Scholar 

  16. Stanley, E. F. & Cox, C. Ann. NY Acad. Sci. 635, 70–79 (1991).

    Article  ADS  CAS  Google Scholar 

  17. Mochida, S., Saisu, H., Kobayashi, H. & Abe, T. Neuroscience 65, 905–915 (1995).

    Article  CAS  Google Scholar 

  18. Rossetto, O. et al. Nature 372, 415–416 (1994).

    Article  ADS  CAS  Google Scholar 

  19. Williamson, L. C., Halpern, J. L., Montecucco, C., Brown, J. E. & Neale, E. A. J. Biol. Chem. 271, 7694–7699 (1996).

    Article  CAS  Google Scholar 

  20. Foran, P., Lawrence, G. W., Shone, C. C., Foster, K. A. & Dolly, J. O. Biochemistry 35, 2630–2636 (1996).

    Article  CAS  Google Scholar 

  21. Sheng, Z.-H., Rettig, L., Cook, T. & Catterall, W. A. Nature 379, 451–454 (1996).

    Article  ADS  CAS  Google Scholar 

  22. Blasi, J. et al. EMBO J. 12, 4821–4828 (1993).

    Article  CAS  Google Scholar 

  23. Shiavo, G., Rossetto, O., Benfenati, F., Poulain, B. & Montecucco, C. Ann. NY Acad. Sci. 710, 65–75 (1994).

    Article  ADS  Google Scholar 

  24. Kee, Y. & Scheller, R. H. J. Neurosci. 16, 1975–1981 (1996).

    Article  CAS  Google Scholar 

  25. Chapman, E. R., Hanson, P. I., An, S. & Jahn, R. J. Biol. Chem. 270, 23667–23671 (1995).

    Article  CAS  Google Scholar 

  26. Wiser, O., Bennett, M. K. & Atlas, D. EMBO J. 15, 4100–4110 (1996).

    Article  CAS  Google Scholar 

  27. Bezprozvanny, I., Scheller, R. H. & Tsien, R. W. Nature 378, 623–626 (1995).

    Article  ADS  CAS  Google Scholar 

  28. Schiavo, G., Shone, C. C., Bennett, M. K., Scheller, R. H. & Montecucco, C. J. Biol. Chem. 270, 10566–10570 (1995).

    Article  CAS  Google Scholar 

  29. Simon, S. M. & Llinas, R. R. Biophys. J. 48, 485–498 (1985).

    Article  ADS  CAS  Google Scholar 

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Authors and Affiliations

  1. Synaptic Mechanisms Section, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bld 36, Rm 5A25, Bethesda, Maryland, 20892, USA

    E. F. Stanley & R. R. Mirotznik

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  1. E. F. Stanley
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  2. R. R. Mirotznik
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Stanley, E., Mirotznik, R. Cleavage of syntaxin prevents G-protein regulation of presynaptic calcium channels. Nature 385, 340–343 (1997). https://doi.org/10.1038/385340a0

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  • DOI: https://doi.org/10.1038/385340a0

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