Mutations in Recessive Congenital Ichthyoses Illuminate the Origin and Functions of the Corneocyte Lipid Envelope.

Abstract

The corneocyte lipid envelope (CLE), a monolayer of ω-hydroxyceramides whose function(s) remain(s) uncertain, is absent in patients with autosomal recessive congenital ichthyoses with mutations in enzymes that regulate epidermal lipid synthesis. Secreted lipids fail to transform into lamellar membranes in certain autosomal recessive congenital ichthyosis epidermis, suggesting the CLE provides a scaffold for the extracellular lamellae. However, because cornified envelopes are attenuated in these autosomal recessive congenital ichthyoses, the CLE may also provide a scaffold for subjacent cornified envelope formation, evidenced by restoration of cornified envelopes after CLE rescue. We provide multiple lines of evidence that the CLE originates as lamellar body-limiting membranes fuse with the plasma membrane: (i) ABCA12 patients and Abca12-/- mice display normal CLEs; (ii) CLEs are normal in Netherton syndrome, despite destruction of secreted LB contents; (iii) CLEs are absent in VSP33B-negative patients; (iv) limiting membranes of lamellar bodies are defective in lipid-synthetic autosomal recessive congenital ichthyoses; and (v) lipoxygenases, lipase activity, and LIPN co-localize within putative lamellar bodies.

• Authors: Debra Crumrine, Denis Khnykin, Peter Krieg, Mao-Qiang Man, Anna Celli, Theodora M Mauro, Joan S Wakefield, Gopinathan Menon, Elizabeth Mauldin, Jeffrey H Miner, Meei-Hua Lin, Alan R Brash, Eli Sprecher, Franz P W Radner, Keith Choate, Dennis Roop, Yoshikazu Uchida, Robert Gruber, Matthias Schmuth, Peter M Elias
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 139 Issue 4 Pg. 760-768 (04 2019) ISSN: 1523-1747 [Electronic] United States
• PMID: 30471252 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Lipids
• DNA

Topics

• Animals
• DNA (genetics)
• DNA Mutational Analysis
• Humans
• Ichthyosiform Erythroderma, Congenital (genetics, metabolism, pathology)
• Lipid Metabolism (genetics)
• Lipids (genetics)
• Mutation
• Skin (metabolism, pathology)