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| Status |
Public on Nov 07, 2019 |
| Title |
SDR9C7 catalyzes critical dehydrogenation of acylceramides for skin barrier formation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
SDR9C7 encodes an orphan short-chain dehydrogenase/reductase recently found mutated in ichthyosis. In a patient with SDR9C7 mutation and a mouse Sdr9c7 knockout model we show loss of covalent binding of epidermal ceramides to protein, a structural fault in the barrier. For reasons unresolved, protein binding requires lipoxygenase-catalyzed transformations of linoleic acid (18:2) esterified in ω-O-acylceramides. In Sdr9c7-/- epidermis, quantitative LC-MS assays revealed almost complete loss of a species of ω-O-acylceramide esterified with linoleate-9,10-trans-epoxy-11E-13-ketone; other acylceramides related to the lipoxygenase pathway were in higher abundance. Recombinant SDR9C7 catalyzed NAD-dependent dehydrogenation of linoleate 9,10-trans-epoxy-11E-13-alcohol to the corresponding 13-ketone, while ichthyosis mutants were inactive. We propose, therefore, that the critical requirement for lipoxygenases and SDR9C7 is in producing acylceramide containing the 9,10-epoxy-11E-13-ketone, a reactive moiety known for its non-enzymatic coupling to protein. This suggests a novel mechanism for coupling of ceramide to protein and provides important insights into skin barrier formation and pathogenesis.
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| Overall design |
We compared gene expression in Sdr9c7-/- (knockout) epidermis at P0 with Sdr9c7+/+ (wild type) controls. Individual array samples were generated by pooling equal amounts of total RNA derived from skins of 5 animals.
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| Contributor(s) |
Hirabayashi T, Nishito Y, Takeichi T, Akiyama M |
| Citation(s) |
31671075 |
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| Submission date |
Aug 09, 2019 |
| Last update date |
Feb 06, 2020 |
| Contact name |
Tetsuya Hirabayashi |
| Organization name |
Tokyo Metropolitan Institute of Medical Science
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| Lab |
Biomembrane
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| Street address |
2-1-6 Kamikitazawa, Setagaya-ku
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| City |
Tokyo |
| ZIP/Postal code |
156-8506 |
| Country |
Japan |
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| Platforms (1) |
| GPL10333 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Feature Number version) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA559537 |
