Localization of serine racemase and its role in the skin.
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.
Department of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Ran
R
Inoue
Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Yoko
Y
Yoshihisa
Shiseido Innovative Science Research and Development Center, Yokohama, Japan.
Yosuke
Y
Tojo
Shiseido Innovative Science Research and Development Center, Yokohama, Japan.
Chieko
C
Okamura
Shiseido Innovative Science Research and Development Center, Yokohama, Japan.
Yuzo
Y
Yoshida
Shiseido Innovative Science Research and Development Center, Yokohama, Japan.
Jiro
J
Kishimoto
Department of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Xinghua
X
Luan
Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Japan.
Masahiko
M
Watanabe
Department of Structural Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Mineyuki
M
Mizuguchi
Department of Structural Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Yuko
Y
Nabeshima
Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Kenji
K
Hamase
Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Kenji
K
Matsunaga
Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Tadamichi
T
Shimizu
Department of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. Electronic address: hmori@med.u-toyama.ac.jp.
Hisashi
H
Mori
D000818:Animals; D002384:Catalysis; D002454:Cell Differentiation; D004817:Epidermis / Q000378:metabolism / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019998:Racemases and Epimerases / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D012867:Skin / Q000201:enzymology*; D011503:Transglutaminases / Q000378:metabolism; D000099300:Serine Racemase
D019998:Racemases and Epimerases; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D011503:Transglutaminases; D000099300:Serine Racemase; C498713:Tgm3 protein, mouse