Abstract
Synaptic vesicle docking and fusion are mediated by the assembly of a stable SNARE core complex of proteins, which include the synaptic vesicle membrane protein VAMP/synaptobrevin and the plasmalemmal proteins syntaxin and SNAP–25. We have now identified another SNAP–25–binding protein, called Snapin. Snapin was enriched in neurons and exclusively located on synaptic vesicle membranes. It associated with the SNARE complex through direct interaction with SNAP–25. Binding of recombinant Snapin–CT to SNAP–25 blocked the association of the SNARE complex with synaptotagmin. Introduction of Snapin–CT and peptides containing the SNAP–25 binding sequence into presynaptic superior cervical ganglion neurons in culture reversibly inhibited synaptic transmission. These results suggest that Snapin is an important component of the neurotransmitter release process through its modulation of the sequential interactions between the SNAREs and synaptotagmin.
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Acknowledgements
We thank Q. Lao for help with the yeast two–hybrid system, X. Zheng for help with synaptosome fractionation, M Takahashi for antibodies, P.A. Roche for SNAP–23 cDNA and S. C. Landis, H. Gainer, R. D. G. McKay, M. Mayer, H. Arnheiter and J. Rettig for comments on the manuscript. This work was supported by the intramural research program of NINDS, NIH (J.M.I and Z.–H.S.), HHMI–NIH Research Scholars Program (J.M.I.), grants from The Japanese Ministry of Education, Science and Culture (S.M.) and the Human Frontier Science Program (S.M.).
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Ilardi, J., Mochida, S. & Sheng, ZH. Snapin: a SNARE–associated protein implicated in synaptic transmission . Nat Neurosci 2, 119–124 (1999). https://doi.org/10.1038/5673
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DOI: https://doi.org/10.1038/5673
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