Cellular and Molecular Life Sciences CMLS

, Volume 62, Issue 17, pp 1984–1995

The peptidylarginine deiminases expressed in human epidermis differ in their substrate specificities and subcellular locations

  • M. C. Méchin
  • M. Enji
  • R. Nachat
  • S. Chavanas
  • M. Charveron
  • A. Ishida-Yamamoto
  • G. Serre
  • H. Takahara
  • M. Simon
Research Article

Abstract.

Deimination, a post-translational modification catalyzed by peptidylarginine deiminases (PADs), appears as a crucial Ca2+-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.

Key words.

Post-translational modification skin keratinocyte differentiation calcium citrulline 

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Copyright information

© Birkhäuser Verlag, Basel 2005

Authors and Affiliations

  • M. C. Méchin
    • 1
  • M. Enji
    • 2
  • R. Nachat
    • 1
  • S. Chavanas
    • 1
  • M. Charveron
    • 3
  • A. Ishida-Yamamoto
    • 4
  • G. Serre
    • 1
  • H. Takahara
    • 2
  • M. Simon
    • 1
  1. 1.UMR 5165, Faculté de MédecineCNRS-University of Toulouse IIIToulouseFrance
  2. 2.Department of Applied Biological Resource Sciences, School of AgricultureIbaraki UniversityIbarakiJapan
  3. 3.Institut de Recherche Pierre FabreToulouseFrance
  4. 4.Department of DermatologyAsahikawa Medical CollegeAsahikawaJapan

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