Changing pattern of deiminated proteins in developing human epidermis

J Invest Dermatol. 2003 May;120(5):817-22. doi: 10.1046/j.1523-1747.2003.12138.x.


Peptidylarginine deiminases are widely distributed, calcium-ion-dependent enzymes that convert arginine residues of proteins into citrulline residues. This reaction, deimination, is thought to be an important event during the final stage of epidermal differentiation, possibly associated with integration and disintegration of keratin filaments. To elucidate the possible roles of protein deimination during human epidermal development we investigated localization of deiminated proteins using anti-citrulline peptide antibody, which preferentially recognizes citrulline residues in the V subdomains of keratin 1, and anti-chemically modified citrulline antibody, which enables detection of citrulline residues independent of amino acid sequences. Anti-chemically modified citrulline antibody, but not anti-citrulline peptide antibody stained the periderm in two-layered epidermis of 49 d and 57 d estimated gestational age. In the stratified epidermis of 88 d, 96 d, and 108 d estimated gestational age fetal skin, anti-citrulline peptide antibody and anti-chemically modified citrulline antibody staining was seen in the periderm and intermediate cell layers. After periderm cells regressed and keratinization began in the interfollicular epidermis, anti-citrulline peptide antibody and anti-chemically modified citrulline antibody were restricted to the cornified cell layers of the interfollicular epidermis, similar to the distribution patterns of that in adult epidermis. Postembedding immunoelectron microscopy showed anti-citrulline peptide antibody immunogold labeling over the cytoplasmic intermediate filament network in the periderm and the intermediate cell layers. These results demonstrate an orderly formation of deiminated proteins in different layers of embryonic epidermis and suggest important roles for peptidylarginine deiminases in human epidermal morphogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cytoplasm / metabolism
  • Epidermal Cells*
  • Epidermis / embryology
  • Epidermis / metabolism
  • Fibroblasts / metabolism
  • Humans
  • Hydrolases / chemistry
  • Immunohistochemistry
  • Keratins / metabolism
  • Microscopy, Fluorescence
  • Microscopy, Immunoelectron
  • Models, Biological
  • Peptides / chemistry
  • Protein-Arginine Deiminase Type 4
  • Protein-Arginine Deiminases
  • Time Factors
  • Tumor Cells, Cultured


  • Peptides
  • Keratins
  • Hydrolases
  • PADI4 protein, human
  • Protein-Arginine Deiminase Type 4
  • Protein-Arginine Deiminases