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Hemifusion arrest by complexin is relieved by Ca2+–synaptotagmin I

Nature Structural & Molecular Biology volume 13, pages 748–750 (2006)Cite this article

Abstract

Synaptic transmission relies on an exquisitely orchestrated series of protein-protein interactions. Here we show that fusion driven by neuronal SNAREs is inhibited by the regulatory protein complexin. Furthermore, inner-leaflet mixing is strongly impaired relative to total lipid mixing, indicating that inhibition by complexin arrests fusion at hemifusion. When the calcium sensor synaptotagmin is added in the presence of calcium, inhibition by complexin is relieved and full fusion rapidly proceeds.

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Figure 1: Ca2+-sytI releases complexin-mediated hemifusion arrest.
Figure 2: Drosophila Cpx (DmCpx) and sytI bind simultaneously to SNARE complexes.
Figure 3: SNARE complex formation, hemifusion arrest by complexin and relief by calcium-synaptotagmin.

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Acknowledgements

The authors thank J. Liao for a preliminary complexin construct, S. Liu for Sso1p protein and members of the McNew laboratory, B. Bartel, M. Gustin, M. Stern and R. Gomer for helpful comments. This work was supported by grants from the US National Science Foundation (IBN-0212605 to J.A.M.), the Robert A. Welch Foundation (C-1517 to J.A.M.) and the US National Institutes of Health (GM051290 to Y.-K.S.)

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Author notes

  1. Johanna R Schaub, Xiaobing Lu and Blair Doneske: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Cell Biology, Rice University, 6100 Main Street MS-140, Houston, 77005, Texas, USA

    Johanna R Schaub, Blair Doneske & James A McNew

  2. Department of Biochemistry, Biophysics, and Molecular Biology, 4152 Molecular Biology Bldg., Iowa State University, Ames, 50011, Iowa, USA

    Xiaobing Lu & Yeon-Kyun Shin

Authors
  1. Johanna R Schaub
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  2. Xiaobing Lu
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Correspondence to James A McNew.

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Supplementary information

Supplementary Fig. 1

Complexin alignment (PDF 945 kb)

Supplementary Fig. 2

Complexins inhibit SNARE-mediated fusion in vitro (PDF 878 kb)

Supplementary Fig. 3

Complexin inhibition is specific for neuronal SNAREs (PDF 542 kb)

Supplementary Methods (PDF 154 kb)

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Schaub, J., Lu, X., Doneske, B. et al. Hemifusion arrest by complexin is relieved by Ca2+–synaptotagmin I. Nat Struct Mol Biol 13, 748–750 (2006). https://doi.org/10.1038/nsmb1124

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