Skip to main content

Thank you for visiting nature.com. 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:

Insertion of diphtheria toxin into and across membranes: role of phosphoinositide asymmetry

Abstract

Diphtheria toxin (DT), a 63,000-molecular weight soluble protein, is toxic to most mammalian cells. The mechanism of intoxication involves a step in which one part of the molecule inserts into a membrane, facilitating the transport of the enzymatic fragment of the protein into the cytoplasm1,2. This event requires an acidic environment and seems to occur at the membrane of an endocytic vesicle3,4. Different cell lines and species differ in their sensitivities to DT—this is due at least in part to differences in the number of DT surface receptors on the cells5, but may also arise from differences in the membrane transport step. It is generally recognized that protein–lipid interactions are of critical importance in membrane transport phenomena (see ref. 6). Thus, it is of interest to determine whether the interaction of DT with membranes is modulated by their composition. We have shown previously that DT interacts with planar lipid bilayers at acidic pH to produce voltage-dependent channels7. We report here that this interaction of DT with bilayers depends on membrane phospholipid composition; the interaction is optimal when inositides are present within the membrane, and the inositides are required on the side of the membrane opposite to that in which DT is introduced.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Collier, R. J. Bact. Rev. 39, 54–85 (1975).

    CAS  Google Scholar 

  2. Pappenheimer, A. M. A. Rev. Biochem. 46, 69–94 (1977).

    Article  CAS  Google Scholar 

  3. Draper, R. K. & Simon, M. I. J. Cell Biol. 87, 849–854 (1980).

    Article  CAS  Google Scholar 

  4. Sandvig, K. & Olsnes, S. J. Cell Biol. 87, 828–832 (1980).

    Article  CAS  Google Scholar 

  5. Middlebrook, J. L., Dorland, R. B. & Leppla, S. H. J. biol. Chem. 254, 7325–7330 (1979).

    Google Scholar 

  6. Parsegian, A. (ed.) Proc. 3rd Biophys. Discussions (1982); Biophys. J. 37, 1–401 (1982).

  7. Donovan, J. J., Simon, M. I., Draper, R. K. & Montal, M. Proc. natn. Acad. Sci. U.S.A. 78, 172–176 (1981).

    Article  ADS  CAS  Google Scholar 

  8. Alving, C. R. et al. Proc. natn. Acad. Sci. U.S.A. 77, 1986–1990 (1980).

    Article  ADS  CAS  Google Scholar 

  9. Miller, C. & Racker, E. J. Membrane Biol. 26, 319–333 (1976).

    Article  CAS  Google Scholar 

  10. O'Brien, D., Costa, L. F. & Ott, R. A. Biochemistry 16, 1295–1303 (1977).

    Article  CAS  Google Scholar 

  11. Kagan, B. L., Finkelstein, A. & Colombini, M. Proc. natn. Acad. Sci. U.S.A. 78, 4950–4954 (1981).

    Article  ADS  CAS  Google Scholar 

  12. Drazin, R., Kandel, J. & Collier, R. J. J. biol. Chem. 246, 1504–1510 (1971).

    CAS  Google Scholar 

  13. Friedman, R. L., Iglewski, B. H., Roerdink, F. & Alving, C. R. Biophys. J. 37, 23–24 (1982).

    Article  CAS  Google Scholar 

  14. Middlebrook, J. L. & Dorland, R. B. Can. J. Microbiol. 25, 285–290 (1979).

    Article  CAS  Google Scholar 

  15. Lory, S. & Collier, R. J. Proc. natn. Acad. Sci. U.S.A. 77, 267–271 (1980).

    Article  ADS  CAS  Google Scholar 

  16. Inouye, M. & Halegoua, S. CRC crit. Rev. Biochem., 339–371 (1980).

  17. Ito, K., Mandel, G. & Wickner, W. Proc. natn. Acad. Sci. U.S.A. 76, 1199–1203 (1979).

    Article  ADS  CAS  Google Scholar 

  18. Ito, K., Date, T. & Wickner, W. J. biol. Chem. 225, 2123–2130 (1980).

    Google Scholar 

  19. Blobel, G. Proc. natn. Acad. Sci. U.S.A. 77, 1496–1500 (1980).

    Article  ADS  CAS  Google Scholar 

  20. Date, T., Goodman, J. M. & Wickner, W. Proc. natn. Acad. Sci. U.S.A. 77, 4669–4673 (1980).

    Article  ADS  CAS  Google Scholar 

  21. Engelman, D. M. & Steitz, T. A. Cell 23, 411–422 (1981).

    Article  CAS  Google Scholar 

  22. Skehel, J. J. et al. Proc. natn. Acad. Sci. U.S.A. 79, 968–972 (1982).

    Article  ADS  CAS  Google Scholar 

  23. Montal, M. Meth. Enzym. 32 B, 545–554 (1974).

    Article  CAS  Google Scholar 

  24. Labarca, P., Coronado, R. & Miller, C. J. gen. Physiol. 76, 397–424 (1980).

    Article  CAS  Google Scholar 

  25. Collier, R. J. & Kandel, J. J. biol. Chem. 246, 1496–1503 (1971).

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Donovan, J., Simon, M. & Montal, M. Insertion of diphtheria toxin into and across membranes: role of phosphoinositide asymmetry. Nature 298, 669–672 (1982). https://doi.org/10.1038/298669a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/298669a0

This article is cited by

Comments

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.

Search

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