1. Neuroscience

Synergistic actions of v-SNARE transmembrane domains and membrane-curvature modifying lipids in neurotransmitter release

  1. Madhurima Dhara
  2. Maria Mantero Martinez
  3. Mazen Makke
  4. Yvonne Schwarz
  5. Ralf Mohrmann
  6. Dieter Bruns  Is a corresponding author
  1. University of Saarland, Germany
  2. Otto-von-Guericke University, Germany
https://doi.org/10.7554/eLife.55152
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  1. Madhurima Dhara
  2. Maria Mantero Martinez
  3. Mazen Makke
  4. Yvonne Schwarz
  5. Ralf Mohrmann
  6. Dieter Bruns
(2020)
Synergistic actions of v-SNARE transmembrane domains and membrane-curvature modifying lipids in neurotransmitter release
eLife 9:e55152.
https://doi.org/10.7554/eLife.55152
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Abstract

Vesicle fusion is mediated by assembly of SNARE proteins between opposing membranes. While previous work suggested an active role of SNARE transmembrane domains (TMDs) in promoting membrane merger (Dhara et al., 2016), the underlying mechanism remained elusive. Here, we show that naturally-occurring v-SNARE TMD variants differentially regulate fusion pore dynamics in mouse chromaffin cells, indicating TMD flexibility as a mechanistic determinant that facilitates transmitter release from differentially-sized vesicles. Membrane curvature-promoting phospholipids like lysophosphatidylcholine or oleic acid profoundly alter pore expansion and fully rescue the decelerated fusion kinetics of TMD-rigidifying VAMP2 mutants. Thus, v-SNARE TMDs and phospholipids cooperate in supporting membrane curvature at the fusion pore neck. Oppositely, slowing of pore kinetics by the SNARE-regulator complexin-2 withstands the curvature-driven speeding of fusion, indicating that pore evolution is tightly coupled to progressive SNARE complex formation. Collectively, TMD-mediated support of membrane curvature and SNARE force-generated membrane bending promote fusion pore formation and expansion.

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All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Madhurima Dhara

    Institute for Physiology, Center of Integrative Physiology and Molecular Medicine, University of Saarland, Homburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7745-472X

  2. Maria Mantero Martinez

    Institute for Physiology, Center of Integrative Physiology and Molecular Medicine, University of Saarland, Homburg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  3. Mazen Makke

    Institute for Physiology, Center of Integrative Physiology and Molecular Medicine, University of Saarland, Homburg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  4. Yvonne Schwarz

    Institute for Physiology, Center of Integrative Physiology and Molecular Medicine, University of Saarland, Homburg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  5. Ralf Mohrmann

    Institute of Physiology, Otto-von-Guericke University, Magdeburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9279-5071

  6. Dieter Bruns

    Institute for Physiology, Center of Integrative Physiology and Molecular Medicine, University of Saarland, Homburg, Germany
    For correspondence
    dieter.bruns@uks.eu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2497-1878

Funding

Deutsche Forschungsgemeinschaft (SFB 1027)

  • Dieter Bruns

Deutsche Forschungsgemeinschaft (SFB 1027)

  • Ralf Mohrmann

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

Version history

  1. Received: January 14, 2020
  2. Accepted: May 7, 2020
  3. Accepted Manuscript published: May 11, 2020 (version 1)
  4. Version of Record published: May 20, 2020 (version 2)

Copyright

© 2020, Dhara 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. Madhurima Dhara
  2. Maria Mantero Martinez
  3. Mazen Makke
  4. Yvonne Schwarz
  5. Ralf Mohrmann
  6. Dieter Bruns
(2020)
Synergistic actions of v-SNARE transmembrane domains and membrane-curvature modifying lipids in neurotransmitter release
eLife 9:e55152.
https://doi.org/10.7554/eLife.55152

Share this article

https://doi.org/10.7554/eLife.55152

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