The peptidylarginine deiminases expressed in human epidermis differ in their substrate specificities and subcellular locations.
Deimination, a post-translational modification catalyzed by peptidylarginine deiminases (PADs), appears as a crucial Ca(2+)-dependent event in the last steps of epidermal differentiation. In normal human epidermis, where the deiminated proteins are filaggrin and keratins, PAD1, 2 and 3 are expressed but their relative role is unknown. The three PADs, produced as active recombinant forms, showed distinct synthetic-substrate specificities, various efficiencies to deiminate filaggrin and particular calcium and pH sensitivities. Immunoelectron microscopy demonstrated that PAD1 and PAD3 are co-located with filaggrin within the filamentous matrix of the deeper corneocytes where the protein is deiminated. This result strongly suggests that both isoforms are involved in the deimination of filaggrin, an essential step leading to free amino acid production necessary for epidermal barrier function. Moreover, PAD1 was shown to persist up to the upper corneocytes where it deiminates keratin K1, a modification supposed to be related to ultrastructural changes of the matrix.
Méchin
M C
MC
UMR 5165, Faculté de Médecine, CNRS-University of Toulouse III, 37 alleés J. Guesde, 31073, Toulouse, France.
Enji
M
M
Nachat
R
R
Chavanas
S
S
Charveron
M
M
Ishida-Yamamoto
A
A
Serre
G
G
Takahara
H
H
Simon
M
M
D000911:Antibodies, Monoclonal / Q000276:immunology; D002118:Calcium / Q000494:pharmacology; D004817:Epidermis / Q000737:chemistry / Q000201:enzymology*; D000091344:Filaggrin Proteins; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006867:Hydrolases / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D000080062:Protein-Arginine Deiminase Type 1; D000080063:Protein-Arginine Deiminase Type 3; D011994:Recombinant Proteins / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism; D013379:Substrate Specificity
D000911:Antibodies, Monoclonal; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D011994:Recombinant Proteins; D006867:Hydrolases; D000080062:Protein-Arginine Deiminase Type 1; D000080063:Protein-Arginine Deiminase Type 3; D002118:Calcium