Fusion of tethered membranes can be driven by Sec18/NSF and Sec17/αSNAP without HOPS

  1. Hongki Song
  2. William T Wickner  Is a corresponding author
  1. Geisel School of Medicine at Dartmouth, United States

Abstract

Yeast vacuolar membrane fusion has been reconstituted with R, Qa, Qb, and Qc-family SNAREs, Sec17/αSNAP, Sec18/NSF, and the hexameric HOPS complex. HOPS tethers membranes and catalyzes SNARE assembly into RQaQbQc trans-complexes which zipper through their SNARE domains to promote fusion. Previously, we demonstrated that Sec17 and Sec18 can bypass the requirement of complete zippering for fusion (Song et al., 2021), but it has been unclear whether this activity of Sec17 and Sec18 is directly coupled to HOPS. HOPS can be replaced for fusion by a synthetic tether when the three Q-SNAREs are pre-assembled. We now report that fusion intermediates with arrested SNARE zippering, formed with a synthetic tether but without HOPS, support Sec17/Sec18-triggered fusion. This zippering-bypass fusion is thus a direct result of Sec17 and Sec18 interactions: with each other, with the platform of partially zippered SNAREs, and with the apposed tethered membranes. As these fusion elements are shared among all exocytic and endocytic traffic, Sec17 and Sec18 may have a general role in directly promoting fusion.

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Figure 1 - Source Data 1contains the numerical data used to generate figure 1.

Article and author information

Author details

  1. Hongki Song

    Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3761-5434
  2. William T Wickner

    Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, United States
    For correspondence
    Bill.Wickner@Dartmouth.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8431-0468

Funding

National Institute of General Medical Sciences (R35GM118037)

  • William T Wickner

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

Reviewing Editor

  1. Adam Linstedt, Carnegie Mellon University, United States

Version history

  1. Preprint posted: August 6, 2021 (view preprint)
  2. Received: August 24, 2021
  3. Accepted: October 25, 2021
  4. Accepted Manuscript published: October 26, 2021 (version 1)
  5. Version of Record published: November 1, 2021 (version 2)
  6. Version of Record updated: November 11, 2021 (version 3)

Copyright

© 2021, Song & Wickner

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. Hongki Song
  2. William T Wickner
(2021)
Fusion of tethered membranes can be driven by Sec18/NSF and Sec17/αSNAP without HOPS
eLife 10:e73240.
https://doi.org/10.7554/eLife.73240

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