Optical manipulation of sphingolipid biosynthesis using photoswitchable ceramides
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 wit...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2019-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/43230 |
| _version_ | 1811181108544405504 |
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| author | Matthijs Kol Ben Williams Henry Toombs-Ruane Henri G Franquelim Sergei Korneev Christian Schroeer Petra Schwille Dirk Trauner Joost CM Holthuis James A Frank |
| author_facet | Matthijs Kol Ben Williams Henry Toombs-Ruane Henri G Franquelim Sergei Korneev Christian Schroeer Petra Schwille Dirk Trauner Joost CM Holthuis James A Frank |
| author_sort | Matthijs Kol |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:14:08Z |
| format | Article |
| id | doaj.art-9b17e632cfa1497dab898c15f108afac |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:14:08Z |
| publishDate | 2019-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-9b17e632cfa1497dab898c15f108afac2022-12-22T04:32:25ZengeLife Sciences Publications LtdeLife2050-084X2019-02-01810.7554/eLife.43230Optical manipulation of sphingolipid biosynthesis using photoswitchable ceramidesMatthijs Kol0https://orcid.org/0000-0003-3068-6501Ben Williams1https://orcid.org/0000-0003-1483-4981Henry Toombs-Ruane2Henri G Franquelim3https://orcid.org/0000-0001-6229-4276Sergei Korneev4https://orcid.org/0000-0002-1273-5819Christian Schroeer5Petra Schwille6https://orcid.org/0000-0002-6106-4847Dirk Trauner7https://orcid.org/0000-0002-6782-6056Joost CM Holthuis8https://orcid.org/0000-0001-8912-1586James A Frank9https://orcid.org/0000-0001-6705-2540Department of Biology/Chemistry, University of Osnabrück, Osnabrück, GermanyDepartment of Chemistry, Ludwig Maximilians University Munich, Munich, GermanyDepartment of Chemistry, Ludwig Maximilians University Munich, Munich, GermanyDepartment of Cellular and Molecular Biophysics, Max Planck Institute of Biochemistry, Martinsried, GermanyDepartment of Biology/Chemistry, University of Osnabrück, Osnabrück, GermanyDepartment of Biology/Chemistry, University of Osnabrück, Osnabrück, GermanyDepartment of Cellular and Molecular Biophysics, Max Planck Institute of Biochemistry, Martinsried, GermanyDepartment of Chemistry, New York University, New York, United StatesDepartment of Biology/Chemistry, University of Osnabrück, Osnabrück, GermanyThe Vollum Institute, Oregon Health and Science University, Portland, United StatesCeramides 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.https://elifesciences.org/articles/43230atomic force microscopysphingomyelin synthasephotopharmacologyceramideglucosylceramideHeLa cells |
| spellingShingle | Matthijs Kol Ben Williams Henry Toombs-Ruane Henri G Franquelim Sergei Korneev Christian Schroeer Petra Schwille Dirk Trauner Joost CM Holthuis James A Frank Optical manipulation of sphingolipid biosynthesis using photoswitchable ceramides eLife atomic force microscopy sphingomyelin synthase photopharmacology ceramide glucosylceramide HeLa cells |
| title | Optical manipulation of sphingolipid biosynthesis using photoswitchable ceramides |
| title_full | Optical manipulation of sphingolipid biosynthesis using photoswitchable ceramides |
| title_fullStr | Optical manipulation of sphingolipid biosynthesis using photoswitchable ceramides |
| title_full_unstemmed | Optical manipulation of sphingolipid biosynthesis using photoswitchable ceramides |
| title_short | Optical manipulation of sphingolipid biosynthesis using photoswitchable ceramides |
| title_sort | optical manipulation of sphingolipid biosynthesis using photoswitchable ceramides |
| topic | atomic force microscopy sphingomyelin synthase photopharmacology ceramide glucosylceramide HeLa cells |
| url | https://elifesciences.org/articles/43230 |
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