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

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Title: PNPLA1 is a transacylase essential for the generation of the skin barrier lipid ω-O-acylceramide
Authors: Ohno, Yusuke Browse this author
Kamiyama, Nozomi Browse this author
Nakamichi, Shota Browse this author
Kihara, Akio Browse this author →KAKEN DB
Issue Date: 1-Mar-2017
Publisher: Nature Publishing Group
Journal Title: Nature communications
Volume: 8
Start Page: 14610
Publisher DOI: 10.1038/ncomms14610
Abstract: Lipids are the primary components of the skin permeability barrier, which is the body's most powerful defensive mechanism against pathogens. Acylceramide (ω-O-acylceramide) is a specialized lipid essential for skin barrier formation. Here, we identify PNPLA1 as the long-sought gene involved in the final step of acylceramide synthesis, esterification of ω-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 in vitro 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 in vitro 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.
Type: article
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 木原 章雄

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