1. Biochemistry and Chemical Biology
  2. Cell Biology
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Sec17 (α-SNAP) and an SM-tethering complex regulate the outcome of SNARE zippering in vitro and in vivo

  1. Matthew L Schwartz
  2. Daniel P Nickerson
  3. Braden T Lobingier
  4. Rachael L Plemel
  5. Mengtong Duan
  6. Cortney G Angers
  7. Michael Zick
  8. Alexey J Merz  Is a corresponding author
  1. University of Washington School of Medicine, United States
  2. California State University, United States
  3. Geisel School of Medicine at Dartmouth, United States
Research Article
  • Cited 12
  • Views 1,518
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Cite this article as: eLife 2017;6:e27396 doi: 10.7554/eLife.27396

Abstract

Zippering of SNARE complexes spanning docked membranes is essential for most intracellular fusion events. Here we explore how SNARE regulators operate on discrete zippering states. The formation of a metastable trans-complex, catalyzed by HOPS and its SM subunit Vps33, is followed by subsequent zippering transitions that increase the probability of fusion. Operating independently of Sec18 (NSF) catalysis, Sec17 (α-SNAP) either inhibits or stimulates SNARE-mediated fusion. If HOPS or Vps33 are absent, Sec17 inhibits fusion at an early stage. Thus, Vps33/HOPS promotes productive SNARE assembly in the presence of otherwise inhibitory Sec17. Once SNAREs are partially zipped, Sec17 promotes fusion in either the presence or absence of HOPS, but with faster kinetics when HOPS is absent, suggesting that ejection of the SM is a rate-limiting step.

Article and author information

Author details

  1. Matthew L Schwartz

    Department of Biochemistry, University of Washington School of Medicine, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Daniel P Nickerson

    Department of Biology, California State University, San Bernardino, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Braden T Lobingier

    Department of Biochemistry, University of Washington School of Medicine, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Rachael L Plemel

    Department of Biochemistry, University of Washington School of Medicine, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Mengtong Duan

    Department of Biochemistry, University of Washington School of Medicine, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Cortney G Angers

    Department of Biochemistry, University of Washington School of Medicine, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Michael Zick

    Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Alexey J Merz

    Department of Biochemistry, University of Washington School of Medicine, Seattle, United States
    For correspondence
    merza@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2177-6492

Funding

National Institute of General Medical Sciences (GM077349)

  • Alexey J Merz

National Institute of General Medical Sciences (T32 GM07270)

  • Matthew L Schwartz
  • Braden T Lobingier
  • Cortney G Angers

National Institute of General Medical Sciences (GM023377)

  • Michael Zick

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 Medical Center, United States

Publication history

  1. Received: April 1, 2017
  2. Accepted: September 15, 2017
  3. Accepted Manuscript published: September 19, 2017 (version 1)
  4. Version of Record published: October 16, 2017 (version 2)

Copyright

© 2017, Schwartz 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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