title: Ceramide synthesis in the epidermis.
abstract: The epidermis and in particular its outermost layer the stratum corneum provides terrestrial vertebrates with a pivotal defensive barrier against water loss, xenobiotics and harmful pathogens. A vital demand for this epidermal permeability barrier is the lipid-enriched lamellar matrix that embeds the enucleated corneocytes. Ceramides are the major components of these highly ordered intercellular lamellar structures, in which linoleic acid- and protein-esterified ceramides are crucial for structuring and maintaining skin barrier integrity. In this review, we describe the fascinating diversity of epidermal ceramides including 1-O-acylceramides. We focus on epidermal ceramide biosynthesis emphasizing its metabolic and topological requirements and discuss enzymes that may be involved in α- and ω-hydroxylation. Finally, we turn to epidermal ceramide regulation, highlighting transcription factors and liposensors recently described to play crucial roles in modulating skin lipid metabolism and epidermal barrier homeostasis. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier.
authors.affiliation: Lipid Pathobiochemistry Group within Department of Cellular & Molecular Pathology, German Cancer Research Center (dkfz.), Heidelberg, Germany.
authors.forename: Mariona
authors.initials: M
authors.lastname: Rabionet
authors.affiliation: Department of Anatomy and Medical Cell Biology, University of Heidelberg, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Gorgas
authors.affiliation: Lipid Pathobiochemistry Group within Department of Cellular & Molecular Pathology, German Cancer Research Center (dkfz.), Heidelberg, Germany; Instrumental Analytics & Bioanalytics, Technical University of Applied Sciences, Mannheim, Germany. Electronic address: r.sandhoff@dkfz.de.
authors.forename: Roger
authors.initials: R
authors.lastname: Sandhoff
mesh_terms: D000818:Animals; D002518:Ceramides / Q000096:biosynthesis*; D004817:Epidermis / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D006900:Hydroxylation / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology*; D008297:Male; D051379:Mice
chemical_list: D002518:Ceramides
keywords: 1-O-Acylceramides; Autosomal recessive congenital ichthyosis (ARCI); Ceramide synthesis; Epidermis; Omega-esterified ceramides; Skin barrier function