title: Peptidylarginine deiminase isoforms 1-3 are expressed in the epidermis and involved in the deimination of K1 and filaggrin.
abstract: Post-translational conversion of arginine to citrulline residues is catalyzed by peptidylarginine deiminases (PAD). Although the existence of five isoforms of PAD has been reported in rodents and humans, their tissue distribution, substrate specificity, and physiological function have yet to be explored. In the epidermis, deimination of filaggrin and keratins is involved in maintaining hydration of the stratum corneum (SC), and hence the cutaneous barrier function. Here, RT-PCR, western blotting, and confocal microscopy analyses with anti-peptide antibodies highly specific for each of the PAD1-4 demonstrated that only PAD1-3 are expressed in mouse and human epidermis. PAD1 was detected in all layers, including the SC, and PAD2 in all the living layers, whereas PAD3 expression was shown to be restricted to the granular layer and lower SC. Moreover, PAD1 and 3 were observed to co-localize with (pro)filaggrin, and PAD2 to be located at the keratinocyte periphery in the stratum granulosum. We also detected PAD1 in extracts of superficial SC, where K1 is deiminated. Moreover, we showed that PAD1 and 3 are able to modify filaggrin in vitro. These data strongly suggest that each enzyme exerts a specific role in the course of epidermis differentiation.
authors.affiliation: CNRS-University of Toulouse III UMR 5165 Epidermis differentiation and rheumatoid autoimmunity, Institut Fédératif de Recherche 30 (INSERM, CNRS, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier), 31073 Toulouse Cedex, France.
authors.forename: Rachida
authors.initials: R
authors.lastname: Nachat
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Méchin
authors.forename: Hidenari
authors.initials: H
authors.lastname: Takahara
authors.forename: Stéphane
authors.initials: S
authors.lastname: Chavanas
authors.forename: Marie
authors.initials: M
authors.lastname: Charveron
authors.forename: Guy
authors.initials: G
authors.lastname: Serre
authors.forename: Michel
authors.initials: M
authors.lastname: Simon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D015153:Blotting, Western; D000078404:Epidermal Cells; D004817:Epidermis / Q000201:enzymology*; D000091344:Filaggrin Proteins; D006801:Humans; D006867:Hydrolases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000276:immunology / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007633:Keratins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D000080062:Protein-Arginine Deiminase Type 1; D000080063:Protein-Arginine Deiminase Type 3; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D007527:Isoenzymes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007633:Keratins; D006867:Hydrolases; D000080062:Protein-Arginine Deiminase Type 1; D000080063:Protein-Arginine Deiminase Type 3