Optical manipulation of sphingolipid biosynthesis using photoswitchable ceramides

Matthijs Kol, Ben Williams, Henry Toombs-Ruane, Henri G. Franquelim, Sergei Korneev, Christian Schroeer, Petra Schwille, Dirk Trauner, Joost Cm Holthuis, James A. Frank

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere43230
JournaleLife
Volume8
DOIs
StatePublished - Feb 5 2019

Keywords

  • HeLa cells
  • atomic force microscopy
  • biochemistry
  • ceramide
  • chemical biology
  • glucosylceramide
  • photopharmacology
  • sphingomyelin synthase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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