PNPLA1 is a transacylase essential for the generation of the skin barrier lipid ω-O-acylceramide

DOI HANDLE PDF Web Site PubMed 被引用文献41件 参考文献40件 オープンアクセス

書誌事項

公開日
2017-03-01
資源種別
journal article
権利情報
  • https://creativecommons.org/licenses/by/4.0
  • https://creativecommons.org/licenses/by/4.0
DOI
  • 10.1038/ncomms14610
公開者
Springer Science and Business Media LLC

説明

<jats:title>Abstract</jats:title> <jats:p> Lipids are the primary components of the skin permeability barrier, which is the body’s most powerful defensive mechanism against pathogens. Acylceramide ( <jats:italic>ω</jats:italic> - <jats:italic>O</jats:italic> -acylceramide) is a specialized lipid essential for skin barrier formation. Here, we identify <jats:italic>PNPLA1</jats:italic> as the long-sought gene involved in the final step of acylceramide synthesis, esterification of <jats:italic>ω</jats:italic> -hydroxyceramide with linoleic acid, by cell-based assays. We show that increasing triglyceride levels by overproduction of the diacylglycerol acyltransferase DGAT2 stimulates acylceramide production, suggesting that triglyceride may act as a linoleic acid donor. Indeed, the <jats:italic>in vitro</jats:italic> analyses confirm that PNPLA1 catalyses acylceramide synthesis using triglyceride as a substrate. Mutant forms of PNPLA1 found in patients with ichthyosis exhibit reduced or no enzyme activity in either cell-based or <jats:italic>in vitro</jats:italic> assays. Altogether, our results indicate that PNPLA1 is directly involved in acylceramide synthesis as a transacylase, and provide important insights into the molecular mechanisms of skin barrier formation and of ichthyosis pathogenesis. </jats:p>

収録刊行物

  • Nature Communications

    Nature Communications 8 (1), 14610-, 2017-03-01

    Springer Science and Business Media LLC

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