Localization of Serine Racemase and Its Role in the Skin

Autor: Jiro Kishimoto, Masahiko Watanabe, Kenji Matsunaga, Hisashi Mori, Ran Inoue, Chieko Okamura, Yuko Nabeshima, Yosuke Tojo, Yuzo Yoshida, Mineyuki Mizuguchi, Tadamichi Shimizu, Xinghua Luan, Yoko Yoshihisa, Kenji Hamase
Rok vydání: 2014
Předmět:
Zdroj: The Journal of Investigative Dermatology
ISSN: 0022-202X
DOI: 10.1038/jid.2014.22
Popis: 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.
Databáze: OpenAIRE