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Exocytosis at the hair cell ribbon synapse apparently operates without neuronal SNARE proteins

Abstract

SNARE proteins mediate membrane fusion. Neurosecretion depends on neuronal soluble NSF attachment protein receptors (SNAREs; SNAP-25, syntaxin-1, and synaptobrevin-1 or synaptobrevin-2) and is blocked by neurotoxin-mediated cleavage or genetic ablation. We found that exocytosis in mouse inner hair cells (IHCs) was insensitive to neurotoxins and genetic ablation of neuronal SNAREs. mRNA, but no synaptically localized protein, of neuronal SNAREs was present in IHCs. Thus, IHC exocytosis is unconventional and may operate independently of neuronal SNAREs.

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Figure 1: Exocytosis in IHCs is resistant to BoNT attack and genetic ablation of neuronal SNAREs.
Figure 2: Neuronal SNARE proteins are abundant in efferent nerve terminals, but not detected in IHCs by immunohistochemistry.

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Acknowledgements

We thank M.C. Wilson for providing SNAP-25 knockout mice, A. Nystuen for providing lethal-wasting mice, D. Bruns and T.C. Südhof for providing synaptobrevin-2/3 double knockout mice, J. Sørensen for discussion, and A. Leonov and C. Griesinger for DM-Nitrophen. We would like to thank R. Jahn and E. Neher for comments on the manuscript and S. Blume, N. Dankenbrink-Werder and M. Köppler for technical assistance. This work was supported by grants of the Deutsche Forschungsgemeinschaft (800/1-1 to R.N. and MO896 2-1 to T.M.), the Max Planck Society (Tandem-Project to N.B. and T.M.) and by a fellowship of the Alexander von Humboldt Foundation (T.P.).

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Contributions

The study was designed by R.N. and T.M. The experimental work was performed by R.N., J.N., A.V.B., E.R., T.P., T.F. and S.S. T.M., R.N., J.N., E.R., T.P., N.B. and T.B. prepared the manuscript.

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Correspondence to Tobias Moser.

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The authors declare no competing financial interests.

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Supplementary Figures 1–10, Supplementary Tables 1 and 2, and Supplementary Methods (PDF 2047 kb)

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Nouvian, R., Neef, J., Bulankina, A. et al. Exocytosis at the hair cell ribbon synapse apparently operates without neuronal SNARE proteins. Nat Neurosci 14, 411–413 (2011). https://doi.org/10.1038/nn.2774

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