1. Structural Biology and Molecular Biophysics
  2. Neuroscience

Functional Synergy between the Munc13 C-terminal C1 and C2 domains

  1. Xiaoxia Liu
  2. Alpay Burak Seven
  3. Marcial Camacho
  4. Vicotoria Esser
  5. Junjie Xu
  6. Thorsten Trimbuch
  7. Bradley Quade
  8. Lijing Su
  9. Cong Ma
  10. Christian Rosenmund
  11. Josep Rizo  Is a corresponding author
  1. University of Texas Southwestern Medical Center, United States
  2. Charité-Universitätsmedizin Berlin, Germany
  3. Huazhong University of Science and Technology, China
https://doi.org/10.7554/eLife.13696
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Cite this article
  1. Xiaoxia Liu
  2. Alpay Burak Seven
  3. Marcial Camacho
  4. Vicotoria Esser
  5. Junjie Xu
  6. Thorsten Trimbuch
  7. Bradley Quade
  8. Lijing Su
  9. Cong Ma
  10. Christian Rosenmund
  11. Josep Rizo
(2016)
Functional Synergy between the Munc13 C-terminal C1 and C2 domains
eLife 5:e13696.
https://doi.org/10.7554/eLife.13696
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Abstract

Neurotransmitter release requires SNARE complexes to bring membranes together, NSF-SNAPs to recycle the SNAREs, Munc18-1 and Munc13s to orchestrate SNARE complex assembly, and Synaptotagmin-1 to trigger fast Ca2+-dependent membrane fusion. However, it is unclear whether Munc13s function upstream and/or downstream of SNARE complex assembly, and how the actions of their multiple domains are integrated. Reconstitution, liposome-clustering and electrophysiological experiments now reveal a functional synergy between the C1, C2B and C2C domains of Munc13-1, indicating that these domains help bridging the vesicle and plasma membranes to facilitate stimulation of SNARE complex assembly by the Munc13-1 MUN domain. Our reconstitution data also suggest that Munc18-1, Munc13-1, NSF, αSNAP and the SNAREs are critical to form a 'primed' state that does not fuse but is ready for fast fusion upon Ca2+ influx. Overall, our results support a model whereby the multiple domains of Munc13s cooperate to coordinate synaptic vesicle docking, priming and fusion.

Article and author information

Author details

  1. Xiaoxia Liu

    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    No competing interests declared.

  2. Alpay Burak Seven

    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    No competing interests declared.

  3. Marcial Camacho

    Department of Neurophysiology, NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    No competing interests declared.

  4. Vicotoria Esser

    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    No competing interests declared.

  5. Junjie Xu

    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    No competing interests declared.

  6. Thorsten Trimbuch

    Department of Neurophysiology, NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    No competing interests declared.

  7. Bradley Quade

    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    No competing interests declared.

  8. Lijing Su

    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    No competing interests declared.

  9. Cong Ma

    Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
    Competing interests
    No competing interests declared.

  10. Christian Rosenmund

    Department of Neurophysiology, NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    Christian Rosenmund, Reviewing editor, eLife.

  11. Josep Rizo

    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    Jose.Rizo-Rey@UTSouthwestern.edu
    Competing interests
    No competing interests declared.

Reviewing Editor

  1. Axel T Brunger, Stanford University, United States

Ethics

Animal experimentation: Animal welfare committees of Charité Medical University and the Berlin state government Agency for Health and Social Services approved all protocols for animal maintenance and experiments (license no. T 0220/09).

Version history

  1. Received: December 9, 2015
  2. Accepted: May 22, 2016
  3. Accepted Manuscript published: May 23, 2016 (version 1)
  4. Version of Record published: June 29, 2016 (version 2)

Copyright

© 2016, Liu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Xiaoxia Liu
  2. Alpay Burak Seven
  3. Marcial Camacho
  4. Vicotoria Esser
  5. Junjie Xu
  6. Thorsten Trimbuch
  7. Bradley Quade
  8. Lijing Su
  9. Cong Ma
  10. Christian Rosenmund
  11. Josep Rizo
(2016)
Functional Synergy between the Munc13 C-terminal C1 and C2 domains
eLife 5:e13696.
https://doi.org/10.7554/eLife.13696

Share this article

https://doi.org/10.7554/eLife.13696

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