Optical manipulation of sphingolipid biosynthesis using photoswitchable ceramides
- University of Osnabrück, Germany
- Ludwig Maximilians University Munich, Germany
- Max Planck Institute of Biochemistry, Germany
- New York University, United States
- University of Osnabrück, Germany
- Oregon Health and Science University, United States
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting source data file. Source data files have been provided for Figures 4-6.
Article and author information
Author details
Henri G Franquelim
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.
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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Optical manipulation of sphingolipid biosynthesis using photoswitchable ceramides
eLife 8:e43230.
https://doi.org/10.7554/eLife.43230
