Abstract
DURING vertebrate development, many neurons depend for survival and differentiation on their target cells1–3. The best documented mediator of such a retrograde trophic action is the neurotrophin nerve growth factor (NGF)1. NGF and the other known members of the neurotrophin family, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) are conserved as distinct genes over large evolutionary distances4–6. Here we report the cloning of neurotrophin-6 (NT-6), a new mem-ber of this family from the teleost fish Xiphophorus. NT-6 dis-tinguishes itself from the other known neurotrophins in that it is not found as a soluble protein in the medium of producing cells. The addition of heparin (but not chondroitin) effects the release of NT-6 from cell surface and extracellular matrix molecules. Recombinant purified NT-6 has a spectrum of actions similar to NGF on chick sympathetic and sensory neurons, albeit with a lower potency. NT-6 is expressed in the embryonic valvulla cerebelli; expression persists in some adult tissues. The interaction of NT-6 with heparin-binding molecules may modulate its action in the nervous system.
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Levi-Montalcini, R. Science 237, 1154–1162 (1987).
Purves, D. Body and Brain: A Tropic Theory of Neural Connection (Harvard Univ. Press, Cambridge, 1988).
Barde, Y.-A. Neuron 2, 1525–1534 (1989).
Götz, R., Raulf, F. & Schartl, M. J. Neurochem. 59, 432–442 (1992).
Götz, R. & Schartl, M. Comp. Biochem. Physiol. 108C, 1–10 (1994).
Hallböök, F., Ibán̄ez, C. F. & Persson, H. Neuron 6, 845–858 (1991).
Hosaka, M. et al. J. biol. Chem. 266, 12127–12130 (1991).
McDonald, N. Q. et al. Nature 354, 411–414 (1991).
Crawford, J. L., Lipscomb, W. N. & Schellman, C. G. Proc. natn. Acad. Sci. U.S.A. 70, 538–542 (1973).
Meek, J. Eur. J. Morphol. 1, 37–51 (1992).
Ruoslahti, E. & Yamaguchi, Y. Cell 64, 867–869 (1991).
LaRochelle, W. J., May-Siroff, M., Robbins, K. C. & Aaronson, S. A. Genes Dev. 5, 1191–1199 (1991).
Lee, B. A. & Donoghue, D. J. J. Cell Biol. 113, 361–370 (1991).
Östman, A., Andersson, M., Betsholtz, C., Westermark, B. & Heldin, C.-H. Cell Reg. 2, 503–512 (1991).
Higashiyama, S., Lau, K., Besner, G. E., Abraham, J. A. & Klagsbrun, M. J. biol. Chem. 267, 6205–6212 (1992).
Yayon, A., Klagsbrun, M., Esko, J. D., Leder, P. & Ornitz, D. M. Cell 64, 841–848 (1991).
Nurcombe, V., Ford, M. D., Wildschut, J. A. & Bartlett, P. F. Science 260, 103–106 (1993).
Rifkin, D. B. & Moscatelli, D. J. Cell Biol. 109, 1–6 (1989).
Vlodavsky, I., Bar-Shavit, R., Ishai-Michaeli, R., Bashkin, P. & Fuks, Z. Trends biochem. Sci. 168, 268–271 (1991).
Marcey, D. & Nüsslein-Volhard, C. Nature 321, 380–381 (1986).
Powers, D. A. Science 246, 352–358 (1989).
Rossant, J. & Hopkins, N. Genes Dev. 6, 1–13 (1992).
Tavolga, W. N. Bull. Am. Mus. nat. Hist. 94, 161–230 (1949).
Okayama, H. et al. Meth. Enzym. 154, 3–28 (1987).
Krumlauf, R. in Gene Transfer and Expression Protocols (ed. Murray, E. J.) 307–323 (Humana, Clifton, 1991).
Wilkinson, D. G. & Green, J. in Postimplantation Mammalian Embryos: A Practical Approach (eds Copp, A. J. & Cockroft, D. L) 155–171 (IRL, Oxford, 1990).
Götz, R., Kolbeck, R., Lottspeich, F. & Barde, Y.-A. Eur. J. Biochem. 204, 745–749 (1992).
Laemmli, U. K. Nature 227, 680–685 (1970).
Barde, Y.-A., Edgar, D. & Thoenen, H. Proc. natn. Acad. Sci. U.S.A 77, 1199–1203 (1980).
Lindsay, R. M., Thoenen, H. & Barde, Y.-A. Devl Biol. 112, 319–328 (1985).
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Götz, R., Köster, R., Winkler, C. et al. Neurotrophin-6 is a new member of the nerve growth factor family. Nature 372, 266–269 (1994). https://doi.org/10.1038/372266a0
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DOI: https://doi.org/10.1038/372266a0
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