SPRR4, a novel cornified envelope precursor: UV-dependent epidermal expression and selective incorporation into...

The cornified cell envelope (CE), a structure formed in the outermost layers of stratified squamous epithelia, provides a physical barrier against environmental insults. It is composed of several structural proteins, which are irreversibly crosslinked by calcium-activated transglutaminases. The small proline rich proteins (SPRRs) are one set of CE precursors. SPRR4, a novel member of this gene family, displayed very low or undetectable expression levels in normal human skin or other stratified squamous epithelia, but was clearly induced by UV light both in vivo and in vitro. High epidermal expression of SPRR4 was monitored only after chronic UV exposure and was concomitant with a thickening of the stratum corneum, which is believed to provide protection against subsequent damage. The calcium-dependent translocation of an SPRR4-GFP fusion protein to the cell periphery in living keratinocytes and its integration into both rigid and fragile cornified envelopes proved that SPRR4 is a novel CE precursor. Interestingly, after UV irradiation, SPRR4 was selectively incorporated into fragile CEs. Our results show for the first time that UV-induced cornification is accompanied by qualitative changes in CE precursor assembly. SPRR4 is part of an adaptive tissue response to environmental stress, which is likely to compensate for UV induced impairment of the epidermal barrier function.