Abstract
Munc13 proteins are essential in neurotransmitter release, controlling the priming of synaptic vesicles to a release-ready state. The sequences responsible for this priming activity are unknown. Here we identify a large α-helical domain of mammalian Munc13-1 that is autonomously folded and is sufficient to rescue the total arrest in neurotransmitter release observed in hippocampal neurons lacking Munc13s.
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Acknowledgements
We thank T. Südhof for fruitful discussions, H. Deng and R. Nehring for technical support and N. Brose (Max Planck Institute for Experimental Medicine, Gottingen, Germany) for providing the Munc13-1 and Munc13-2 double-knockout mice and the pSFV1-Munc13-1WT-EGFP vector. This work was supported by a grant from the Muscular Dystrophy Association and by US National Institutes of Health grants NS37200 to J.R. and NS51262 to C.R.
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Supplementary information
Supplementary Fig. 1
Munc13-1 fragments that did not fold (PDF 38 kb)
Supplementary Fig. 2
Secondary structure prediction of Munc13-1 (800-1579) (PDF 38 kb)
Supplementary Fig. 3
Purification of the MUN domain (PDF 18 kb)
Supplementary Fig. 4
The MUN domain does not bind syntaxin (PDF 137 kb)
Supplementary Methods
Computational analysis, cell culture and electrophysiology (PDF 28 kb)
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Basu, J., Shen, N., Dulubova, I. et al. A minimal domain responsible for Munc13 activity. Nat Struct Mol Biol 12, 1017–1018 (2005). https://doi.org/10.1038/nsmb1001
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DOI: https://doi.org/10.1038/nsmb1001
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