FIGURE 8.
Scheme of the degradation of filaggrin in mammalian epidermis. Filaggrin (F) is a component of the cornified envelope in the outer layer of the epidermis. It accumulates in the keratohyalin granules as a high molecular weight, extremely insoluble phosphorylated precursor protein (10). During terminal differentiation, the phosphorylated filaggrin (P-F) is dephosphorylated and then proteolytically cleaved to polypeptides (each ∼35 kDa). The enzymatic properties and epidermal localization of PAD1 and/or PAD3 suggest that they are responsible for the deimination of filaggrin (54). As shown in the present study, caspase 14 partially participates in the processing of the deiminated filaggrin (Cit-F) into limited fragments as illustrated by Denecker et al. (16). On the other hand, calpain I preferentially fragments deiminated filaggrin into the smaller peptides, and then these peptides are degraded into free amino acids acting as NMFs by BH in the lower stratum corneum.