PNPLA1 has a crucial role in skin barrier function by directing acylceramide biosynthesis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-03-01

AUTHORS

Tetsuya Hirabayashi, Tatsuki Anjo, Arisa Kaneko, Yuuya Senoo, Akitaka Shibata, Hiroyuki Takama, Kohei Yokoyama, Yasumasa Nishito, Tomio Ono, Choji Taya, Kazuaki Muramatsu, Kiyoko Fukami, Agustí Muñoz-Garcia, Alan R Brash, Kazutaka Ikeda, Makoto Arita, Masashi Akiyama, Makoto Murakami

ABSTRACT

Mutations in patatin-like phospholipase domain-containing 1 (PNPLA1) cause autosomal recessive congenital ichthyosis, but the mechanism involved remains unclear. Here we show that PNPLA1, an enzyme expressed in differentiated keratinocytes, plays a crucial role in the biosynthesis of ω-O-acylceramide, a lipid component essential for skin barrier. Global or keratinocyte-specific Pnpla1-deficient neonates die due to epidermal permeability barrier defects with severe transepidermal water loss, decreased intercellular lipid lamellae in the stratum corneum, and aberrant keratinocyte differentiation. In Pnpla1-/- epidermis, unique linoleate-containing lipids including acylceramides, acylglucosylceramides and (O-acyl)-ω-hydroxy fatty acids are almost absent with reciprocal increases in their putative precursors, indicating that PNPLA1 catalyses the ω-O-esterification with linoleic acid to form acylceramides. Moreover, acylceramide supplementation partially rescues the altered differentiation of Pnpla1-/- keratinocytes. Our findings provide valuable insight into the skin barrier formation and ichthyosis development, and may contribute to novel therapeutic strategies for treatment of epidermal barrier defects. More... »

PAGES

14609

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms14609

    DOI

    http://dx.doi.org/10.1038/ncomms14609

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1084128842

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28248300


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