1. Cell Biology
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Multiple factors maintain assembled trans-SNARE complexes in the presence of NSF and aSNAP

  1. Eric A Prinslow
  2. Karolina P Stepien
  3. Yun-Zu Pan
  4. Junjie Xu
  5. Josep Rizo  Is a corresponding author
  1. University of Texas Southwestern Medical Center, United States
Research Article
  • Cited 19
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Cite this article as: eLife 2019;8:e38880 doi: 10.7554/eLife.38880

Abstract

Neurotransmitter release requires formation of trans-SNARE complexes between the synaptic vesicle and plasma membranes, which likely underlies synaptic vesicle priming to a release-ready state. It is unknown whether Munc18-1, Munc13-1, complexin-1 and synaptotagmin-1 are important for priming because they mediate trans-SNARE complex assembly and/or because they prevent trans-SNARE complex disassembly by NSF-aSNAP, which can lead to de-priming. Here we show that trans-SNARE complex formation in the presence of NSF-aSNAP requires both Munc18-1 and Munc13-1, as proposed previously, and is facilitated by synaptotagmin-1. Our data also show that Munc18-1, Munc13-1, complexin-1 and likely synaptotagmin-1 contribute to maintaining assembled trans-SNARE complexes in the presence of NSF-aSNAP. We propose a model whereby Munc18-1 and Munc13-1 are critical not only for mediating vesicle priming but also for precluding de-priming by preventing trans-SNARE complex disassembly; in this model, complexin-1 also impairs de-priming, while synaptotagmin-1 may assist in priming and hinder de-priming.

Article and author information

Author details

  1. Eric A Prinslow

    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Karolina P Stepien

    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Yun-Zu Pan

    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Junjie Xu

    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Josep Rizo

    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    Jose.Rizo-Rey@UTSouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1773-8311

Funding

National Institute of Neurological Disorders and Stroke (R35 NS097333)

  • Josep Rizo

Welch Foundation (I-1304)

  • Josep Rizo

National Institute of General Medical Sciences (T32 GM008297)

  • Eric A Prinslow

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Axel T Brunger, Stanford University, United States

Publication history

  1. Received: June 3, 2018
  2. Accepted: January 17, 2019
  3. Accepted Manuscript published: January 18, 2019 (version 1)
  4. Version of Record published: January 30, 2019 (version 2)

Copyright

© 2019, Prinslow 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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