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Protein kinase C activity regulates d‐serine availability in the brain
Author(s) -
VargasLopes Charles,
Madeira Caroline,
Kahn Suzana A.,
Albino do Couto Ingrid,
Bado Patricia,
Houzel Jean Christophe,
De Miranda Joari,
de Freitas Marta S.,
Ferreira Sergio T.,
Panizzutti Rogerio
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.07102.x
Subject(s) - serine , phosphorylation , protein kinase c , nmda receptor , kinase , biology , microbiology and biotechnology , biochemistry , chemistry , receptor
J. Neurochem. (2011) 116 , 281–290. Abstract d ‐Serine is a co‐agonist of NMDA receptor (NMDAR) and plays important roles in synaptic plasticity mechanisms. Serine racemase (SR) is a brain‐enriched enzyme that converts l ‐serine to d ‐serine. SR interacts with the protein interacting with C‐kinase 1 (PICK1), which is known to direct protein kinase C (PKC) to its targets in cells. Here, we investigated whether PKC activity regulates SR activity and d ‐serine availability in the brain. In vitro , PKC phosphorylated SR and decreased its activity. PKC activation increased SR phosphorylation in serine residues and reduced d ‐serine levels in astrocyte and neuronal cultures. Conversely, PKC inhibition decreased basal SR phosphorylation and increased cellular d ‐serine levels. In vivo modulation of PKC activity regulated both SR phosphorylation and d ‐serine levels in rat frontal cortex. Finally, rats that completed an object recognition task showed decreased SR phosphorylation and increased d ‐serine/total serine ratios, which was markedly correlated with decreased PKC activity in both cortex and hippocampus. Results indicate that PKC phosphorylates SR in serine residues and regulates d ‐serine availability in the brain. This interaction may be relevant for the regulation of physiological and pathological mechanisms linked to NMDAR function.