Abstract
POLYSIALIC acid (PSA) is a dynamically regulated product of post-translational modification of the neural cell adhesion molecule, NCAM1,2. Presence of the large anionic carbohydrate modulates NCAM binding properties and, by increasing the intercellular space, influences interactions between other cell surface molecules1–5. PSA expression underlies cell type- and developmental-specific alterations6 and correlates with stages of cellular motility6–8. In the adult, PSA becomes restricted to regions of permanent neural plasticity and regenerating neural and muscle tissues6,9,10. Recent data implicate its important function in spatial learning and memory11,12, and in tumour biology13–16. Here we describe the molecular characterization of polysialyltransferase-1, the key enzyme of eukaryotic PSA synthesis. In reconstitution experiments, the newly cloned enzyme induces PSA synthesis in all NCAM-expressing cell lines. Our data therefore represent convincing evidence that the polycondensation of α–2,8–linked sialic acids in mammals is the result of a single enzymatic activity and provide a new basis for studying the functional role of PSA in neuro- and tumour biology.
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References
Hoffman, S. & Edelman, G. M. Proc. natn. Acad. Sci. U.S.A. 80, 5762–5766 (1983).
Rutishauser, U., Acheson, A., Hall, A. K., Mann, D. L. & Sunshine, J. Science 240, 53–57 (1988).
Acheson, A., Sunshine, J. L. & Rutishauser, U. J. Cell Biol. 114, 143–153 (1991).
Yang, P., Yin, X. & Rutishauser, U. J. Cell Biol. 116, 1487–1496 (1992).
Doherty, P., Cohen, J. & Walsh, F. S. Neuron 5, 209–219 (1990).
Edelman, G. M. A. Rev. Cell Biol. 2, 81–116 (1986).
Tang, J., Landmesser, L. & Rutishauser, U. Neuron 8, 1031–1044 (1992).
Landmesser, L. J. Neurobiol. 23, 1131–1139 (1992).
Martini, R. & Schachner, M. J. Cell Biol. 106, 1735–1746 (1988).
Daniloff, J. K., Levi, G., Grumet, M., Rieger, F. & Edelman, G. M. J. Cell Biol. 103, 929–945 (1986).
Cremer, H. et al. Nature 367, 455–459 (1994).
Tomasiewicz, H. et al. Neuron 11, 1163–1174 (1993).
Moolenaar, C. E. C. K. et al. Cancer Res. 50, 1102–1106 (1990).
Takamatzu, K. et al. Cancer Res. 64, 2598–2603 (1994).
Komminoth, P., Roth, J., Lackie, P. M., Bitter-Suermann, D. & Heitz, P. U. Am. J. Pathol. 139, 297–304 (1991).
Kern, W. F., Spier, C. M., Miller, T. P. & Grogan, T. M. Leukemia Lymphoma 12, 1–10 (1993).
McCoy, R. D., Vimr, E. R. & Troy, F. A. J. biol. Chem. 260, 12659–12699 (1984).
Kitazume, S., Kitajima, K., Inoue, S., Inoue, Y. & Troy, F. A. J. biol. Chem. 269, 10330–10340 (1994).
Block, R. J. J. Cell Biol. 116, 449–463 (1992).
Frosch, M., Görgen, I., Boulnois, G. J., Timmis, K. N. & Bitter-Suermann, D. Proc. natn. Acad. Sci. U.S.A. 82, 1194–1198 (1985).
Bierhuizen, M. F. A., Mattei, M.-G. & Fukuda, M. Genes Dev. 7, 468–478 (1993).
Seed, B. & Aruffo, A. Proc. natn. Acad. Sci. U.S.A. 84, 3365–3369 (1987).
Häyrinen, J., Bitter-Suermann, D. & Finne, J. Molec. Immun. 26, 523–529 (1989).
Drickamer, K. Glycobiology 3, 2–3 (1993).
Klein, P., Kanehisa, M. & DeLisi, C. Biochim. biophys. Acta 815, 468–471 (1985).
Livingston, B. D. & Paulson, J. C. J. biol. Chem. 268, 11504–11507 (1993).
Nara, K. et al. Proc. natn. Acad. Sci. U.S.A. 91, 7952–7956 (1994).
Sasaki, K. et al. J. biol. Chem. 269, 15950–15956 (1994).
Higgins, D. G. & Scharp, P. M. Gene 73, 237–244 (1988).
Tomlinson, S. & Taylor, P. W. J. Virol. 55, 374–378 (1985).
Gerardy-Schahn, R. & Eckhardt, M. Int. J. Cancer 8 (suppl.), 38–42 (1994).
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Eckhardt, M., Mühlenhoff, M., Bethe, A. et al. Molecular characterization of eukaryotic polysialyltransferase-1. Nature 373, 715–718 (1995). https://doi.org/10.1038/373715a0
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DOI: https://doi.org/10.1038/373715a0
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