Assembly of the epidermal cornified cell envelope

Abstract

The cornified cell envelope structure is formed beneath the plasma membrane in terminally differentiating stratified squamous epithelia. It provides a vital physical barrier to these tissues in mammals and consists of a 10 nm thick layer of highly crosslinked insoluble proteins. In the specialized case of the epidermis, a 5 nm thick layer of ceramide lipids is covalently bound to the proteins. These organize extracellular lipids into orderly lamellae and, together, the cell envelope and extracellular lipids are essential for effective physical and water barrier function in the skin.The assembly of the cornified cell envelope proceeds in three principal stages, starting in the upper spinous cell layers of the epidermis.As intracellular Ca2+ levels rise in suprabasal cells, envoplakin (green), periplakin (red) and involucrin (blue) are expressed. Envoplakin and periplakin form stable heterotetramers, and in vitro data have shown that involucrin and envoplakin-periplakin heterotetramers associate with the plasma membrane in a Ca2+-dependent manner. Coincidently, the transglutaminase 1 enzyme (purple) is expressed, and it spontaneously assembles onto membranes by way of its acyl lipid adducts. As intracellular (or localized micro-environmental) Ca2+ levels continue to rise, the enzyme joins together the plakins and involucrin by forming Nϵ-(γ-glutamyl)lysine isopeptide crosslinks. The enzyme also crosslinks other membrane-associated and desmosomal proteins, which drastically chan…