Localization of Serine Racemase and Its Role in the Skin

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.

Gut microbiota–derived D-serine protects against acute kidney injury

“…gut were the primary microbial products (12) and that they played physiologic roles in the central nervous system (13), heart (14), and skin (15). However, the precise roles of the gut microbiota-associated D-amino acids in kidney diseases have yet to be revealed.…”

Nuclear Compartmentalization of Serine Racemase Regulates d-Serine Production

“…Rabbit anti-seven in absentia homologue (Siah) (1:500) was a gift from Dr. Simone Engelender (Technion-Israel Institute of Technology) and has been described in earlier studies (38,39). Rabbit affinity-purified anti-SR antibody (0.2-0.3 g/ml) (18) or guinea pig anti-SR have also been described elsewhere (40). Anti-rabbit, anti-mouse, and anti-guinea pig peroxide-conjugated IgG (1:20,000) was purchased from Jackson ImmunoResearch.…”

“…Two micrograms of purified rabbit anti-SR antibody were added by overnight rotation at 4°C, and SR was immunoprecipitated with protein A magnetic beads. The beads were washed six times with the immunoprecipitation buffer, and SR was probed with guinea pig anti-SR, as described previously (40). Co-immunoprecipitation with lamin was revealed with mouse anti-lamin A/C.…”

Neurohumoral mechanisms of keratinocytes regulation in diabetes mellitus

“…На кератиноцитах также экспонированы NMDA-глута мат ные рецепторы (ионотропный рецептор глутамата, селективно связывающий N-метил-D-аспартат), чьим эндогенным коагонистом является D-серин, при этом конверсия неактивного l-серина в активный D-серин с помощью серин-рацемазы может осуществляться в самих кератиноцитах. Было показано, что NMDA-рецепторы в коже участвуют в регуляции пролиферации и дифференцировки, а также в формировании эпителиального барьера, однако их роль на настоящий момент до конца не изучена [37]. Холинергическая система В кератиноцитах существует и так называемая не-нейрональная холинергическая система.…”