Abstract
After binding to specific membrane receptors of target neurones and responsive phaeochromocytoma cells, nerve growth factor (NGF) is internalized and accumulated in the perikaryon within membrane-confined compartments (H. Rohrer et al., unpublished observation, and refs 1–5). Although quantitative electron microscopic autoradiography and ultrahistochemical studies gave no evidence for further movement of NGF1,2,4,5, it was claimed on the basis of light microscopy of PC12 cells (ref. 6 and P.C. Marchisio, personal communication) that some of the NGF taken up by the cell reaches the free cytoplasm and subsequently the nucleus where it would exert a physiological effect. We report here that the direct introduction of NGF into the free cytoplasm of phaeochromocytoma cells by fusion with NGF-loaded erythrocyte ghosts does not induce fibre outgrowth, in contrast to the normal response of these cells seen when NGF is added to the culture medium. Correspondingly, NGF antibodies introduced into the cytoplasm do not prevent fibre outgrowth evoked by NGF added to the culture medium. Thus, the binding of NGF to its receptor must result in the production of a second messenger either from the cell surface or after internalization from an intracellular compartment7,8.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Schwab, M. & Thoenen, H. Brain Res. 122, 459–474 (1977).
Schwab, M. Brain Res. 130, 190–196 (1977).
Levi, A., Schechter, Y., Neufeld, E. J. & Schlessinger, J. Proc. natn. Acad. Sci. U.S.A. 77, 3469–3473 (1980).
Claude, Ph., Dunis, D. A. & Hawrot, E. J. Cell Biol. 83, 632 (1979).
Schwab, M., Suda, K. & Thoenen, H. J. Cell Biol. 72, 798–810 (1979).
Marchisio, P. C., Naldini, L. & Calissano, P. Proc. natn. Acad. Sci. U.S.A. 77, 1656–1660 (1980).
Thoenen, H. & Barde, Y.-A. Physiol. Rev. 60, 1284–1335 (1980).
Thoenen, H., Schäfer, Th., Heumann, R. & Schwab, M. in Hormones and Cell Regulation Vol. 5 (eds Dumont, J. E. & Nunez, J.) 15–34 (Elsevier, Amsterdam, 1981).
Yamaizumi, M., Uchida, T., Mekada, E. & Okada, Y. Cell 18, 1009–1014 (1979).
Schlegel, R. A. & Mercer, W. E. in Introduction of Macromolecules into Viable Mammalian Cells (eds Baserga, R., Croce, C. & Rovera, G.) 145–155 (Liss, New York, 1980).
Greene, L. A. J. Cell Biol. 78, 747–755 (1978).
Calissano, P. & Cozzari, C. Proc. natn. Acad. Sci. U.S.A. 71, 2131–2135 (1974).
Levi, A., Cimino, M., Mercanti, D., Chen, J. S. & Calissano, P. Biochim. biophys. Acta 399, 50–60 (1975).
Calissano, P., Monaco, G., Castellani, L., Mercanti, D. & Levi, A. Proc. natn. Acad. Sci. U.S.A. 75, 2210–2214 (1978).
Andres, R. Y., Jeng, J. & Bradshaw, R. A. Proc. natn. Acad. Sci. U.S.A. 74, 2785–2789 (1977).
Pappenheimer, A. M. Jr & Gill, D. M. Science 182, 353–358 (1973).
Collier, J. R. Bact. Rev. 39, 54–85 (1975).
Mazurkiewicz, J. E. & Nakane, P. K. J. Histochem. Cytochem. 20, 969–974 (1972).
Sutter, A., Riopelle, R. J., Harris-Warrick, R. M. & Shooter, E. M. J. biol. Chem. 254, 5972–5982 (1979).
Valet, G., Hofmann, H. & Ruhenstroth-Bauer, G. J. Histochem. Cytochem. 24, 231–246 (1976).
Stockel, K., Gagnon, C., Guroff, G. & Thoenen, H. J. Neurochem. 26, 1207–1211 (1976).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Heumann, R., Schwab, M. & Thoenen, H. A second messenger required for nerve growth factor biological activity?. Nature 292, 838–340 (1981). https://doi.org/10.1038/292838a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/292838a0
This article is cited by
-
Neurotrophins as synaptic modulators
Nature Reviews Neuroscience (2001)
-
Signal transduction from membrane to nucleus: The special case for neurons
Neurochemical Research (1996)
-
The concept of uptake and retrograde transport of neurotrophic molecules during development: History and present status
Neurochemical Research (1996)
-
Inhibition of exocytosis by intracellularly applied antibodies against a chromaffin granule-binding protein
Nature (1989)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.