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Initial events of myelination involve Fyn tyrosine kinase signalling

Abstract

MYELIN is the lipoprotein multimembrane that functions as an insulator preventing the flow of ion currents across the axonal membrane and facilitating the conduction of nerve impulses. It is synthesized by oligodendrocytes in the central nervous system at about the time of birth in mammals1. During the initial stages of myelination, several proteins are phosphorylated on tyrosine. Among these proteins, we identified Fyn tyrosine kinase, one of the non–receptor–type tyrosine kinases of the Src family. Here we report that Fyn tyrosine kinase is activated during the initial stages of myelination and that it is associated with the large myelin–associated glycoprotein (MAG), an adhesion molecule that has been implicated in myelinogenesis2. The Fyn–large MAG association requires amino-terminal domains of Fyn that include SH2 and SH3 (Src homology domains 2 and 3). Crosslinking of large MAG with antibody induces a rapid increase in the specific activity of Fyn kinase. These results indicate that Fyn participates in the initial events of myelination as a signalling molecule downstream of large MAG; indeed, we find that fyndeficient mice exhibit impaired myelination.

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References

  1. Duncan, I. D., Skoff, R. P. & Colman, D. (eds) Myelination and Dysmyelination (New York Academy of Sciences, New York, 1990).

  2. Lemke, G. Neuron 1, 535–543 (1988).

    Article  CAS  Google Scholar 

  3. Norton, W. T. & Poduslo, S. E. J. Neurochem., 21, 749–757 (1973).

    Article  CAS  Google Scholar 

  4. Umemori, H. et al. Molec. Brain Res. 16, 303–310 (1992).

    Article  CAS  Google Scholar 

  5. Cooper, J. A. in Peptides and Protein Phosphorylation (ed. Kemp, B.) 85–113 (CRC Press, Boca Raton, 1990).

    Google Scholar 

  6. Salzer, J. L., Holmes, W. P. & Colman, D. R. J. Cell Biol. 104, 957–965 (1987).

    Article  CAS  Google Scholar 

  7. Sternberger, N. H., Quarles, R. H., Itoyama, Y. & Webster, H. de F. Proc. natn. Acad. Sci. U.S.A. 76, 1510–1514 (1979).

    Article  ADS  CAS  Google Scholar 

  8. Johnson, P. W. et al. Neuron 3, 377–385 (1989).

    Article  CAS  Google Scholar 

  9. Poltrak, M. et al. J. Cell Biol. 105, 1893–1899 (1987).

    Article  Google Scholar 

  10. Edwards, A. M. et al. Molec. cell. Biol. 8, 2655–2658 (1988).

    Article  CAS  Google Scholar 

  11. Veillette, A., Bookman, M. A., Horak, E. M. & Bolen, J. B. Cell 55, 301–308 (1988).

    Article  CAS  Google Scholar 

  12. Samelson, L. E., Phillips, A. F., Luong, E. T. & Klausner, R. D. Proc. natn. Acad. Sci. U.S.A. 87, 4358–4362 (1990).

    Article  ADS  CAS  Google Scholar 

  13. Yamanashi, Y., Kakiuchi, T., Mizuguchi, J., Yamamoto, T. & Toyoshima, K. Science 251, 192–194 (1991).

    Article  ADS  CAS  Google Scholar 

  14. Eiseman, E. & Bolen, J. B. Nature 355, 78–80 (1992).

    Article  ADS  CAS  Google Scholar 

  15. Hatakeyama, M. et al. Science 252, 1523–1528 (1991).

    Article  ADS  CAS  Google Scholar 

  16. Sudol, M., Grant, S. G. N. & Maisonpierre, P. C. Neurochem. Inc. 22, 369–384 (1993).

    Article  CAS  Google Scholar 

  17. Koch, C. A., Anderson, D., Moran, M. F., Ellis, C. & Pawson, T. Science 252, 668–674 (1991).

    Article  ADS  CAS  Google Scholar 

  18. Yagi, T. et al. Nature 366, 742–745 (1993).

    Article  ADS  CAS  Google Scholar 

  19. Grant, S. G. N. et al. Science 258, 1903–1910 (1992).

    Article  ADS  CAS  Google Scholar 

  20. Yamanashi, Y. et al. Proc. natn. Acad. Sci. U.S.A. 89, 1118–1122 (1992).

    Article  ADS  CAS  Google Scholar 

  21. Okada, M., Nada, S., Yamanashi, Y., Yamamoto, T. & Nakagawa, H. J. biol. Chem. 266, 24249–24252 (1991).

    CAS  PubMed  Google Scholar 

  22. Fujita, N. et al. J. Neurochem. 55, 1056–1059 (1990).

    Article  CAS  Google Scholar 

  23. Sukegawa, J. et al. Oncogene 5, 611–614 (1990).

    CAS  PubMed  Google Scholar 

  24. Parsons, S. J., McCarley, D. J., Raymond, V. W. & Parsons, J. T. J. Virol. 59, 755–758 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Fujita, N. et al. Biochem. biophys. Res. Commun. 165, 1162–1169 (1989).

    Article  CAS  Google Scholar 

  26. Semba, K. et al. Proc natn. Acad. Sci. U.S.A. 83, 5459–5463 (1986).

    Article  ADS  CAS  Google Scholar 

  27. Tanaka, A. et al. Molec. cell. Biol. 7, 1978–1983 (1987).

    Article  CAS  Google Scholar 

  28. Takebe, Y. et al. Molec. cell. Biol. 8, 466–472 (1988).

    Article  CAS  Google Scholar 

  29. Turner, J. M. et al. Cell 60, 755–765 (1990).

    Article  CAS  Google Scholar 

  30. Kunkel, T. A. Proc. natn. Acad. Sci. U.S.A. 82, 488–492 (1985).

    Article  ADS  CAS  Google Scholar 

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Umemori, H., Satot, S., Yagi, T. et al. Initial events of myelination involve Fyn tyrosine kinase signalling. Nature 367, 572–576 (1994). https://doi.org/10.1038/367572a0

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