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

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 and Makoto Murakami ()
Additional contact information
Tetsuya Hirabayashi: Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science
Tatsuki Anjo: Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science
Arisa Kaneko: Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science
Yuuya Senoo: Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences
Akitaka Shibata: Nagoya University Graduate School of Medicine
Hiroyuki Takama: Nagoya University Graduate School of Medicine
Kohei Yokoyama: Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science
Yasumasa Nishito: Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science
Tomio Ono: Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science
Choji Taya: Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science
Kazuaki Muramatsu: School of Science and Engineering, Tokyo Denki University
Kiyoko Fukami: Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences
Agustí Muñoz-Garcia: Ecology, and Organismal Biology, Ohio State University
Alan R. Brash: Vanderbilt Institute of Chemical Biology, Vanderbilt University
Kazutaka Ikeda: Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences
Makoto Arita: Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences
Masashi Akiyama: Nagoya University Graduate School of Medicine
Makoto Murakami: Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms14609 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14609

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms14609

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().