Hornerin, a novel profilaggrin-like protein and differentiation-specific marker isolated from mouse skin.
A novel mouse cDNA named hornerin was isolated by RNA differential display applied to developing mouse skin. Hornerin, which has 2,496 amino acids, comprises EF-hand domains at the N terminus followed by a spacer sequence and a large repetitive domain, indicating that hornerin is a novel member of the "fused gene"-type cornified envelope precursor protein family. The repetitive domain of hornerin was found to be rich in glycine, serine, and glutamine. Hornerin was expressed in the tongue, esophagus, forestomach, and skin among the adult mouse tissues examined, all of them cornifying stratified epithelium. In the embryonic mouse skin, hornerin mRNA was first detected on gestational day 15.5 in the epidermis coincidentally with the formation of a granular layer. In accordance with this, hornerin was detected in the granular and cornified layers of the mature epidermis. In the granular cells of the epidermis, the hornerin protein was detected in keratohyalin granules together with profilaggrin. Furthermore, Western blot analysis of the mouse skin showed that the hornerin protein was cleaved during the process of epidermal differentiation, indicating possible posttranslational proteolytic processing as is observed in profilaggrin. Differentiation of primary mouse epidermal keratinocytes with 0.12 mm Ca(2+) resulted in the induction of hornerin. These results indicate that hornerin is structurally as well as functionally most similar to profilaggrin among the family members and possibly plays pleiotropic roles, including a role in cornification.
Makino
T
T
Department of Dermatology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama-shi 930-0194, Japan.
Takaishi
M
M
Morohashi
M
M
Huh
N H
NH
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D020832:EF Hand Motifs; D004591:Electrophoresis, Polyacrylamide Gel; D004817:Epidermis / Q000378:metabolism; D004947:Esophagus / Q000378:metabolism; D000091344:Filaggrin Proteins; D005753:Gastric Mucosa / Q000378:metabolism; D020869:Gene Expression Profiling; D015723:Gene Library; D017403:In Situ Hybridization; D007381:Intermediate Filament Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000737:chemistry*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000196:embryology* / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution; D014059:Tongue / Q000378:metabolism
D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D000091344:Filaggrin Proteins; C503909:Hrnr protein, mouse; D007381:Intermediate Filament Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D012313:RNA; D002118:Calcium