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The VASE exon downregulates the neurite growth-promoting activity of NCAM 140

Nature volume 356, pages 791–793 (1992)Cite this article

Abstract

AXONAL growth, guidance and synapse formation are controlled by receptors on neuronal growth cones that can recognize positive and inhibitory cues in the local microenvironment1–3. Four well characterized receptor systems are known that recognize the growth-promoting activities associated with the extracellular matrix and the membranes of cells such as astrocytes, muscle cells and Schwann cells; these are the integrins4and the homophilically binding cell adhesion molecules neural-cell adhesion molecule (NCAM), N-cadherin and LI (refs 5-12). Alternative splicing generates 20-30 isoforms of NCAM and these can also be differentially glycosylated13. There are two sites where alternative splicing changes the extracellular structure of membrane-bound NCAM and one of these (the MSD1 region) does not obviously affect function6. Here we report that the variable alternatively spliced exon (VASE) in immunoglobulin domain 4 downregulates the neurite outgrowth-promoting activity of NCAM. The high level of VASE expression in the adult central as compared with peripheral nervous system21 could contribute to the poor regenerative capacity of the former.

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References

  1. Dodd, J. & Jessell, T. M. Science 242, 692–699 (1988).

    Article  ADS  CAS  Google Scholar 

  2. Strittmatter, S. M. & Fishman, M. C. BioEssays 13, 127–134 (1991).

    Article  CAS  Google Scholar 

  3. Doherty, P. & Walsh, F. S. Curr. Opinion Cell Biol. 1, 1102–1106 (1989).

    Article  CAS  Google Scholar 

  4. Reichardt, L. F. Tomaselli, K. J. A. Rev. Neurosci. 14, 531–570 (1991).

    Article  CAS  Google Scholar 

  5. Bixby, J. L., Pratt, R. S., Lilien, J. & Reichardt, L. F. Proc. natn. Acad. Sci. U.S.A. 84, 2555–2559 (1987).

    Article  ADS  CAS  Google Scholar 

  6. Doherty, P. et al. Nature 343, 464–466 (1990).

    Article  ADS  CAS  Google Scholar 

  7. Takeichi, M. Science 251, 1451–1455 (1991).

    Article  ADS  CAS  Google Scholar 

  8. Doherty, P., Rowett, L. H., Moore, S. E., Mann, D. A. & Walsh, F. S. Neuron 6, 247–258 (1991).

    Article  CAS  Google Scholar 

  9. Lemmon, V., Farr, K. L. & Lagenaur, C. Neron 2, 1597–1603 (1989).

    Article  CAS  Google Scholar 

  10. Doherty, P., Cohen, J. & Walsh, F. S. Neuron 5, 209–219 (1990).

    Article  CAS  Google Scholar 

  11. Inuzuka, H., Miyatani, S. & Takeichi, M. Neuron 7, 69–79 (1991).

    Article  CAS  Google Scholar 

  12. Seilheimer, B. & Schachner, M. J. Cell Biol. 107, 341–351 (1988).

    Article  CAS  Google Scholar 

  13. Finne, J., Finne, U., Deagostini-Bazin, H. & Goridis, C. Biochem. biophys. Res. Commun. 112, 482–487 (1983).

    Article  CAS  Google Scholar 

  14. Cunningham, B. A. et al. Science 236, 799–806 (1987).

    Article  ADS  CAS  Google Scholar 

  15. Walsh, F. S. & Doherty, P. Semin. Neurosci. 3, 271–284 (1991).

    Article  Google Scholar 

  16. Dickson, G. et al. Cell 50, 1119–1130 (1987).

    Article  CAS  Google Scholar 

  17. Prediger, E. A., Hoffman, S., Edelman, G. M. & Cunningham, B. A. Proc. natn. Acad. Sci. U.S.A. 85, 9616–9620 (1988).

    Article  ADS  CAS  Google Scholar 

  18. Small, S. J., Haines, S. L. & Akeson, R. A. Neuron 1, 1007–1017 (1988).

    Article  CAS  Google Scholar 

  19. Santoni, M. J. et al. EMBO J. 8, 385–392 (1989).

    Article  CAS  Google Scholar 

  20. Gower, H. J. et al. Cell 55, 955–964 (1988).

    Article  CAS  Google Scholar 

  21. Small, S. J. & Akeson, R. J. Cell Biol. 111, 2089–2096 (1990).

    Article  CAS  Google Scholar 

  22. Hoffman, S. & Edelman, G. M. Proc. natn. Acad. Sci. U.S.A. 80, 5762–5766 (1983).

    Article  ADS  CAS  Google Scholar 

  23. Rutishauser, U., Acheson, A., Hall, A. K., Mann, D. M. & Sunshine, J. Science 240, 53–57 (1988).

    Article  ADS  CAS  Google Scholar 

  24. Doherty, P., Ashton, S. V., Moore, S. E. & Walsh, F. S. Cell 67, 21–33 (1991).

    Article  CAS  Google Scholar 

  25. Pizzey, J., Rowett, L. H., Barton, C. H., Dickson, G. & Walsh, F. S. J. Cell Biol. 109, 3465–3476 (1989).

    Article  CAS  Google Scholar 

  26. Kadmon, G., Kowitz, A., Altevogt, P. & Schachner, M. J. Cell Biol. 110, 193–208 (1990).

    Article  CAS  Google Scholar 

  27. Cole, G. L., Loewy, A. & Glaser, L. Nature 320, 445–447 (1986).

    Article  ADS  CAS  Google Scholar 

  28. Chuong, C.-M. & Edelman, G. M. J. Neurosci. 4, 2354–2368 (1984).

    Article  CAS  Google Scholar 

  29. Patel, K. et al. Br. J. Cancer 63 (suppl. XIV) 20–23 (1991).

    Google Scholar 

  30. Moolenaar, C. E. C., Pieneman, C., Walsh, F. S., Mooi, W. J. & Michalides, R. J. A. M. Int. J. Cancer (in the press).

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Author notes

  1. C. E. C. Kitty Moolenaar and Rob J. A. M. Michalides: Department of Tumour Biology, The Netherlands Cancer Institute, Plesmanlaan 121,1066 CX Amsterdam, The Netherlands

Authors and Affiliations

  1. Department of Experimental Pathology, UMDS, Guy's Hospital, London Bridge, London, SE19RT, UK

    Patrick Doherty, C. E. C. Kitty Moolenaar,  Ashton, Rob J. A. M. Michalides & Frank S. Walsh

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  1. Patrick Doherty
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Doherty, P., Moolenaar, C., Ashton et al. The VASE exon downregulates the neurite growth-promoting activity of NCAM 140. Nature 356, 791–793 (1992). https://doi.org/10.1038/356791a0

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