Skip to main content
SpringerLink
Log in

Essential functions of synapsins I and II in synaptic vesicle regulation

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

SYNAPTIC vesicles are coated by synapsins, phosphoproteins that account for 9% of the vesicle protein1-3. To analyse the functions of these proteins, we have studied knockout mice lacking either synapsin I, synapsin II, or both. Mice lacking synapsins are viable and fertile with no gross anatomical abnormalities, but experience seizures with a frequency proportional to the number of mutant alleles. Synapsin-II and double knockouts, but not synapsin-I knockouts, exhibit decreased post-tetanic potentiation and severe synaptic depression upon repetitive stimulation. Intrinsic synaptic-vesicle membrane proteins, but not peripheral membrane proteins or other synaptic proteins, are slightly decreased in individual knockouts and more severely reduced in double knockouts, as is the number of synaptic vesicles. Thus synapsins are not required for neurite outgrowth, synaptogenesis or the basic mechanics of synaptic vesicle traffic, but are essential for accelerating this traffic during repetitive stimulation. The phenotype of the synapsin knockouts could be explained either by deficient recruitment of synaptic vesicles to the active zone, or by impaired maturation of vesicles at the active zone, both of which could lead to a secondary destabilization of synaptic vesicles.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Huttner, W. B., Schiebler, W., Greengard, P. & De Camilli, P. J. Cell Biol. 96, 1374–1388 (1983).

    Article  CAS  Google Scholar 

  2. De Camilli, P., Benfenati, F., Valtorta, F. & Greengard, P. A. Rev. Cell Biol. 6, 433–460 (1990).

    Article  CAS  Google Scholar 

  3. Südhof, T. C. et al. Science 245, 1474–1480 (1989).

    Article  ADS  Google Scholar 

  4. Rosahl, T. W. et al. Cell 75, 661–670 (1993).

    Article  CAS  Google Scholar 

  5. Imaizumi, K. et al. Jikken Dobutsu (Bull. exp. Anim.) 8, 6–10 (1959).

    Google Scholar 

  6. Baines, A. J. & Bennett, V. Nature 315, 410–413 (1985).

    Article  ADS  CAS  Google Scholar 

  7. Petrucci, T. C. & Morrow, J. J. Cell Biol. 105, 1355–1363 (1987).

    Article  CAS  Google Scholar 

  8. Bähler, M. & Greengard, P. Nature 326, 704–707 (1987).

    Article  ADS  Google Scholar 

  9. Steiner, J. P., Ling, E. & Bennett, V. J. biol. Chem. 262, 905–914 (1987).

    CAS  PubMed  Google Scholar 

  10. Greengard, P., Valtorta, F., Czernik, A. J. & Benfenati, F. Science 259, 780–785 (1993).

    Article  ADS  CAS  Google Scholar 

  11. Rusakov, D. A., Skibo, G. G. & Vasilenko, D. A. Neurosci. Lett. 131, 156–158 (1991).

    Article  CAS  Google Scholar 

  12. Hess, S. D., Doroshenko, P. A. & Augustine, G. J. Science 259, 1169–1172 (1993).

    Article  ADS  CAS  Google Scholar 

  13. Geppert, M. et al. Nature 369, 493–497 (1994).

    Article  ADS  CAS  Google Scholar 

  14. Zucker, R. S. A. Rev. Neurosci. 12, 13–31 (1989).

    Article  CAS  Google Scholar 

  15. McCormick, D. A., Connors, B. W., Lighthall, J. W. & Prince, D. A. J. Neurophysiol. 54, 782–806 (1985).

    Article  CAS  Google Scholar 

  16. Mandell, J. W. et al. Neuron 5, 19–33 (1990).

    Article  CAS  Google Scholar 

  17. Geppert, M. et al. EMBO J. 13, 3720–3727 (1994).

    Article  CAS  Google Scholar 

  18. Missler, M., Wolff, A., Merker, H.-J. & Wolff, J. R. J. comp. Neurol. 333, 53–67 (1993).

    Article  CAS  Google Scholar 

  19. Weibel, E. R. Stereological Methods (Academic, New York, 1979).

    Google Scholar 

  20. Woolson, R. F. in Statistical Methods for the Analysis of Biochemical Data 344–347 (Wiley, New York, 1987).

    Google Scholar 

  21. Li, C. et al. Neuron 13, 885–898 (1994).

    Article  CAS  Google Scholar 

  22. Robertson, E. J. in Teratocarcinomas and embryonic stem cells (ed. Robertson, E. J.) 71 112 (IRL, Oxford, 1987).

    Google Scholar 

  23. Soriano, P., Montgomery, C., Geske, R. & Bradley, A. Cell 64, 693–702 (1991).

    Article  CAS  Google Scholar 

  24. Adams, J. C. J. Histochem. Cytochem. 29, 775 (1981).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Genetics, The University of Texas Southwestern Medical School, Dallas, Texas, 75235, USA

    Thomas W. Rosahl, Markus Missler, Joachim Herz & Thomas C. Südhof

  2. Department of Biochemistry, The University of Texas Southwestern Medical School, Dallas, Texas, 75235, USA

    Robert E. Hammer

  3. Howard Hughes Medical Institute, The University of Texas Southwestern Medical School, Dallas, Texas, 75235, USA

    Thomas W. Rosahl, Markus Missler, Robert E. Hammer & Thomas C. Südhof

  4. Departments of Psychiatry and Physiology, Center for Neurobiology and Psychiatry, University of California at San Francisco, San Francisco, California, 94143, USA

    Diane Spillane, David K. Selig & Robert C. Malenka

  5. Zentrum Anatomie, Universität Göttingen, 37075, Göttingen, Germany

    Markus Missler & Joachim R. Wolff

Authors
  1. Thomas W. Rosahl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Diane Spillane
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Markus Missler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joachim Herz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David K. Selig
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joachim R. Wolff
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Robert E. Hammer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Robert C. Malenka
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Thomas C. Südhof
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rosahl, T., Spillane, D., Missler, M. et al. Essential functions of synapsins I and II in synaptic vesicle regulation. Nature 375, 488–493 (1995). https://doi.org/10.1038/375488a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/375488a0

  • Springer Nature Limited

This article is cited by

Search

Navigation