Abstract
TETANUS toxin inhibits neurotransmitter release by selectively blocking fusion of synaptic vesicles1,2. Recently tetanus toxin was shown to proteolytically degrade synaptobrevin II (also named VAMP-2), a synaptic vesicle-specific protein3,4, in vitro and in nerve terminals5,6. As targets of tetanus toxin, synaptobrevins probably function in the exocytotic fusion of synaptic vesicles. Here we describe a new synaptobrevin homologue, cellubrevin, that is present in all cells and tissues tested and demonstrate that it is a membrane trafficking protein of a constitutively recycling pathway. Like synaptobrevin II, cellubrevin is proteolysed by tetanus toxin light chain in vitro and after transfection. Our results suggest that constitutive and regulated vesicular pathways use homologous proteins for membrane trafficking, probably for membrane fusion at the plasma membrane, indicating a greater mechanistic and evolutionary similarity between these pathways than previously thought.
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References
Simpson, L. L. (ed.) Botulinum Neurotoxin and Tetanus Toxin (Academic, San Diego, 1989).
Niemann, H. in A Sourcebook of Bacterial Protein Toxins (eds Alouf, J. E. & Freer, J. H.) 303–348 (Academic, San Diego, 1991).
Südhof, T. C. & Jahn, R. Neuron 6, 665–677 (1991).
Trimble, W. S., Linial, M. & Scheller, R. A. Rev. Neurosci. 14, 665–677 (1991).
Schiavo, G. et al. Nature 359, 832–835 (1992).
Link, E. et al. Biochem. Biophys. Res. Commun. 189, 1017–1023 (1992).
Burgess, T. L. & Kelly, R. B. A. Rev. Cell Biol. 3, 243–293 (1987).
Huttner, W. B. & Dotti, C. G. Curr. Opin. Neurobiol. 1, 388–392 (1991).
Hubbard, A. L. Curr. Opin. Cell Biol. 1, 675–683 (1989).
Smythe, E. & Warren, G. Europ. J. Biochem. 202, 689–699 (1991).
Regnier-Vigouroux, A., Tooze, S. A. & Huttner, W. B. EMB0 J. 10, 3589–3601 (1991).
Dotti, C. G. & Simons, K. Cell 62, 63–72 (1990).
Johnston, P. A. et al. EMB0 J. 8, 2863–2872 (1989).
Cameron, P. L., Südhof, T. C., Jahn, R. & De Camilli, P. J. Cell Biol. 115, 151–164 (1991).
Linstedt, A. D. & Kelly, R. B. Neuron 7, 309–317 (1991).
Marsal, J., Egea, G., Solsona, C., Rabasseda, X. & Blasi, J. Proc. natn. Acad. Sci. U.S.A. 86, 372–376 (1989).
Südhof, T. C., Baumert, M., Perin, M. S. & Jahn, R. Neuron 2, 1474–1481 (1989).
Trimble, W. S., Cowan, D. M. & Scheller, R. H. Proc. natn. Acad. Sci. U.S.A. 85, 4538–4542 (1988).
Elferink, L. A., Trimble, W. S. & Scheller, R. H. J. biol. Chem. 264, 11061–11064 (1989).
Archer, B. T., Ozcelik, T., Jahn, R., Francke, U. & Südhof, T. C. J. biol. Chem. 265, 17267–17273 (1990).
Südhof, T. C. J. biol. Chem. 265, 1988–1992 (1990).
Südhof, T. C., Lottspeich, F., Greengard, P., Mehl, E. & Jahn, R. Science 238, 1142–1144 (1987).
Bordier, C. J. biol. Chem. 256, 1604–1607 (1981).
Burger, P. M. et al. Neuron 3, 715–720 (1989).
Gorman, D. in DNA Cloning Vol. 2 (ed. Glover, D. M.) 143–190 (IRL, Oxford, 1985).
Maycox, P. R., Link, E., Reetz, A., Morris, S. A. & Jahn, R. J. Cell Biol. 118, 1379–1388 (1992).
Eisel, U. et al. EMBO J. 5, 2495–2502 (1986).
Fairweather, N. J. & Lyness, V. A. Nucleic Acids Res. 14, 7809–7812 (1986).
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McMahon, H., Ushkaryov, Y., Edelmann, L. et al. Cellubrevin is a ubiquitous tetanus-toxin substrate homologous to a putative synaptic vesicle fusion protein. Nature 364, 346–349 (1993). https://doi.org/10.1038/364346a0
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DOI: https://doi.org/10.1038/364346a0
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