FIGURE 15.4 • Schematic diagram of keratinocytes in the epidermis. The keratinocytes in this figure reflect different stages in the life cycle of the cell as it passes from the basal layer to the skin surface, where it becomes desquamated. The basal cell begins to synthesize intermediate (keratin) filaments; these are grouped into bundles and are seen in the light microscope as tonofibrils. The cell enters the spinous layer, where the synthesis of intermediate filaments continues. In the upper part of the spinous layer, the cells begin to produce keratohyalin granules containing intermediate filament–associated proteins and glycolipid-containing lamellar bodies. Within the granular layer, the cell discharges lamellar bodies that contribute to formation of the water barrier of the epidermis; the remainder of the cell cytoplasm contains numerous keratohyalin granules that, in close association with tonofilaments, form the cell envelope. The surface cells are keratinized; they contain a thick cell envelope and bundles of tonofilaments in a specialized matrix. Desquamation of keratinized cells is controlled by pH that monitors KLK activity and its interaction with LEKTI. Keratinocytes positioned near the granular layer exhibit neutral pH, which maintains desmosomal interactions and allows a strong interaction in the extracellular matrix between LEKTI and its KLK targets. As the pH acidifies toward the skin surface, LEKTI and KLK dissociate, allowing proteinase to activate and search for other protein targets in the extracellular space. In the most superficial layers of keratinocytes, pH is low enough for active KLK molecules to digest desmosomal proteins. In concert with other proteinase activities, this action leads to a complete degradation of desmosomal junctions, resulting in the detachment of the most superficial layer of keratinocytes. rER, rough-surfaced endoplasmic reticulum.
FIGURE 15.5 • Schematic diagram of the epidermal water barrier. The heterogeneous mixture of glycosphingolipids, phospholipids, and ceramides makes up the lamellae of the lamellar bodies. The lamellar bodies, produced within the Golgi apparatus, are secreted by exocytosis into the intercellular spaces between the stratum granulosum and stratum corneum, where they form the lipid envelope. The lamellar arrangement of lipid molecules is depicted in the intercellular space just below the thickened plasma membrane and forms the cell envelope of the keratinized keratinocyte. The innermost part of the cell envelope consists primarily of loricrin molecules (pink spheres) that are cross-linked by small proline-rich (SPR) proteins and elafin. The layer adjacent to the cytoplasmic surface of the plasma membrane consists of the two tightly packed proteins involucrin and cystatin . Keratin filaments (tonofilaments) bound by filaggrin are anchored into the cell envelope.
involved in formation of the cornified envelope, desquamation of cornified cells, and antimicrobial  defenses in the skin. The epidermal water barrier thus consists of two structural elements:  The cell envelope (CE) is a 15-nm-thick layer of insoluble proteins deposited on the inner surface of the plasma membrane that contributes to the strong mechanical properties of the barrier. The thickness of the CE increases in epithelia that are subject to considerable mechanical stress (e.g., lip, palm of the hand, sole of the foot). The CE is formed by cross-linking small prolinerich (SPR) proteins and larger structural proteins. The structural proteins include cystatin, desmosomal proteins (desmoplakin), elafn, envoplakin, flaggrin, involucrin, five different keratin chains, and loricrin.
Loricrin is the major structural protein and accounts for almost 80% of the total CE protein mass. This 26-kilodalton insoluble protein has the highest glycine content of any known protein in the body.