Localization of Serine Racemase and Its Role in the Skin

Ran Inoue, Yoko Yoshihisa, Yosuke Tojo, Chieko Okamura, Yuzo Yoshida, Jiro Kishimoto, Xinghua Luan, Masahiko Watanabe, Mineyuki Mizuguchi, Yuko Nabeshima, Kenji Hamase, Kenji Matsunaga, Tadamichi Shimizu, Hisashi Mori

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19 Citations (Scopus)

Abstract

D-Serine is an endogenous coagonist of the N-methyl-D-aspartate (NMDA)-type glutamate receptor in the central nervous system and its synthesis is catalyzed by serine racemase (SR). Recently, the NMDA receptor has been found to be expressed in keratinocytes (KCs) of the skin and involved in the regulation of KC growth and differentiation. However, the localization and role of SR in the skin remain unknown. Here, using SR-knockout (SR-KO) mice as the control, we demonstrated the localization of the SR protein in the granular and cornified layer of the epidermis of wild-type (WT) mice and its appearance in confluent WT KCs. We also demonstrated the existence of a mechanism for conversion of L-serine to D-serine in epidermal KCs. Furthermore, we found increased expression levels of genes involved in the differentiation of epidermal KCs in adult SR-KO mice, and alterations in the barrier function and ultrastructure of the epidermis in postnatal day 5 SR-KO mice. Our findings suggest that SR in the skin epidermis is involved in the differentiation of epidermal KCs and the formation of the skin barrier.

Original languageEnglish
Pages (from-to)1618-1626
Number of pages9
JournalJournal of Investigative Dermatology
Volume134
Issue number6
DOIs
Publication statusPublished - Jan 1 2014

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Inoue, R., Yoshihisa, Y., Tojo, Y., Okamura, C., Yoshida, Y., Kishimoto, J., ... Mori, H. (2014). Localization of Serine Racemase and Its Role in the Skin. Journal of Investigative Dermatology, 134(6), 1618-1626. https://doi.org/10.1038/jid.2014.22