Functional Significance of Protein Deimination during the Cornification of Epidermis

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We previously reported the presence of deiminated keratins and filaggrin in rat epidermis (J.Invest. Dermtol. 105,163-69 (1995) ; supported by Grant-in-Aide 06833012). Here we performed identification of the major deiminated keratin molecule and cloning of peptidylarginine deiminase (PAD) cDNAs. We also conducted comparative studies of protein deimination using various experimental systems.1. Major deiminated proteins in human and mouse epidermis were identified to be partially degraded and disulfide-cross-linked keratin K1 in the cornified layr suggesting the possible role of protein deimination in modulating the interaction of K1 with its partner keratin K10, pre-existent keratins K5/K14 network or keratin-associated proteins.2. Three PAD clones were isolated from a cDNA library of immortalized newbom rat kerationcytes that had been induced to express PAD with retinoic acid. One of them closely resembled skeletal muscle PAD cDNA previously obtained in our laboratory. The other two appeared to be novel cDNAs encoding PADs. Further research is in progress to see if either of them encodes PAD expressed in the epidermis.3. Deimination of keratins and filaggrin in mouse epidermis was found to increase markedly during postnatal few hours. Cultivation of late prenatal embryonic skin suggested that exposure to air is required for normal deimination of these epidermal proteins. Comparative studies using human, rat, mouse, and guine a pig showed significant species differences in filaggrin deimination.