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Snapin: a SNARE–associated protein implicated in synaptic transmission

Nature Neuroscience volume 2, pages 119–124 (1999)Cite this article

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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Figure 1: Molecular cloning of Snapin.
Figure 2: The tissue and subcellular distribution of Snapin.
Figure 3: In–vitro interaction of Snapin with SNAP–25.
Figure 4: Association of Snapin with the SNARE complex in vivo.
Figure 5: Effects of Snapin–CT on synaptic transmission of SCGNs in culture.
Figure 6: Inhibition of binding to SNAP–25 and neurotransmitter release by the Snapin peptides.

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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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Authors and Affiliations

  1. Synaptic Function Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 36, Room 5A23 , 9000 Rockville Pike, Bethesda, 20892, Maryland , USA

    Jeffrey M. Ilardi & Zu-Hang Sheng

  2. Department of Physiology, Tokyo Medical University, Tokyo, 160-8402, Japan

    Sumiko Mochida

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  1. Jeffrey M. Ilardi
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Correspondence to Zu-Hang Sheng.

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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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