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Activity-dependent changes in partial VAMP complexes during neurotransmitter release

Nature Neuroscience volume 2, pages 1078–1083 (1999)Cite this article

Abstract

The temporal sequence of SNARE protein interactions that cause exocytosis is unknown. Blockade of synaptic neurotransmitter release through cleavage of VAMP/synaptobrevin by tetanus toxin light chain (TeNT-LC) was accelerated by nerve stimulation. Botulinum/B neurotoxin light chain (BoNT/B-LC), which cleaves VAMP at the same site as TeNT-LC, did not require stimulation. Because TeNT-LC requires the N-terminal coil domain of VAMP for binding but BoNT/B-LC requires the C-terminal coil domain, it seems that, before nerve activity, the N-terminal domain is shielded in a protein complex, but the C-terminal domain is exposed. This N-terminal complex lasts until nerve activity occurrs and may serve to cock synaptic vesicles for immediate exocytosis upon Ca2+ entry.

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Figure 1: Stimulation accelerates the inhibitory effect of TeNT-LC on EPSP amplitude.
Figure 2: Activity dependence of TeNT-LC.
Figure 3: Nerve activity is required for cleavage of VAMP by TeNT-LC but not by BoNT/B-LC.
Figure 4: VAMP structure and effect of BoNT/B.
Figure 5: Effect of TeNT-LC is blocked by hVAMP2/27-55.
Figure 6: The effect of BoNT/D-LC requires nerve activity.

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Acknowledgements

We thank W. Trimble for TeNT-LC and BoNT/D-LC, A. Zdanovsky for BoNT/B-LC, C. C. Shone for anti-VAMP and H. Bellen for anti-synaptotagmin. We thank M. Salter for assistance with the phosphotyrosine assay.

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  1. Physiology Department, MSB, Rm 3232, University of Toronto, 1 King's College Circle, Ontario, M5S 1A8, Toronto, Canada

    Shao-Ying Hua & Milton P. Charlton

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Correspondence to Shao-Ying Hua.

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Hua, SY., Charlton, M. Activity-dependent changes in partial VAMP complexes during neurotransmitter release. Nat Neurosci 2, 1078–1083 (1999). https://doi.org/10.1038/16005

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