1. Biochemistry and Chemical Biology
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Optical manipulation of sphingolipid biosynthesis using photoswitchable ceramides

  1. Matthijs Kol
  2. Ben Williams
  3. Henry Toombs-Ruane
  4. Henri G Franquelim
  5. Sergei Korneev
  6. Christian Schroeer
  7. Petra Schwille
  8. Dirk Trauner  Is a corresponding author
  9. Joost CM Holthuis  Is a corresponding author
  10. James A Frank  Is a corresponding author
  1. University of Osnabrück, Germany
  2. Ludwig Maximilians University Munich, Germany
  3. Max Planck Institute of Biochemistry, Germany
  4. New York University, United States
  5. University of Osnabrück, Germany
  6. Oregon Health and Science University, United States
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Cite this article as: eLife 2019;8:e43230 doi: 10.7554/eLife.43230

Abstract

Ceramides are central intermediates of sphingolipid metabolism that also function as potent messengers in stress signaling and apoptosis. Progress in understanding how ceramides execute their biological roles is hampered by a lack of methods to manipulate their cellular levels and metabolic fate with appropriate spatiotemporal precision. Here, we report on clickable, azobenzene-containing ceramides, caCers, as photoswitchable metabolic substrates to exert optical control over sphingolipid production in cells. Combining atomic force microscopy on model bilayers with metabolic tracing studies in cells, we demonstrate that light-induced alterations in the lateral packing of caCers lead to marked differences in their metabolic conversion by sphingomyelin synthase and glucosylceramide synthase. These changes in metabolic rates are instant and reversible over several cycles of photoswitching. Our findings disclose new opportunities to probe the causal roles of ceramides and their metabolic derivatives in a wide array of sphingolipid-dependent cellular processes with the spatiotemporal precision of light.

Article and author information

Author details

  1. Matthijs Kol

    Department of Biology/Chemistry, University of Osnabrück, Osnabrück, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3068-6501
  2. Ben Williams

    Department of Chemistry, Ludwig Maximilians University Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Henry Toombs-Ruane

    Department of Chemistry, Ludwig Maximilians University Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Henri G Franquelim

    Department of Cellular and Molecular Biophysics, Max Planck Institute of Biochemistry, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6229-4276
  5. Sergei Korneev

    Department of Biology/Chemistry, University of Osnabrück, Osnabrück, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Christian Schroeer

    Department of Biology/Chemistry, University of Osnabrück, Osnabrück, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Petra Schwille

    Department of Cellular and Molecular Biophysics, Max Planck Institute of Biochemistry, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6106-4847
  8. Dirk Trauner

    Department of Chemistry, New York University, New York, United States
    For correspondence
    dirktrauner@nyu.edu
    Competing interests
    The authors declare that no competing interests exist.
  9. Joost CM Holthuis

    Department of Biology/Chemistry, University of Osnabrück, Osnabrück, Germany
    For correspondence
    Joost.Holthuis@Biologie.Uni-Osnabrueck.DE
    Competing interests
    The authors declare that no competing interests exist.
  10. James A Frank

    The Vollum Institute, Oregon Health and Science University, Portland, United States
    For correspondence
    frankja@ohsu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6705-2540

Funding

Deutsche Forschungsgemeinschaft (SFB1032)

  • Henri G Franquelim
  • Petra Schwille
  • Dirk Trauner
  • James A Frank

National Sciences and Engineering Research Council of Canada

  • Ben Williams

Deutsche Forschungsgemeinschaft (SFB944)

  • Matthijs Kol
  • Joost CM Holthuis

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

Reviewing Editor

  1. Arun Radhakrishnan, University of Texas Southwestern Medical Center, United States

Publication history

  1. Received: October 30, 2018
  2. Accepted: February 2, 2019
  3. Accepted Manuscript published: February 5, 2019 (version 1)

Copyright

© 2019, Kol 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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