Protein kinase C activity regulates d-serine availability in the brain
Article first published online: 16 DEC 2010
Journal of Neurochemistry © 2010 International Society for Neurochemistry. No claim original US government works
Journal of Neurochemistry
Volume 116, Issue 2, pages 281–290, January 2011
How to Cite
Vargas-Lopes, C., Madeira, C., Kahn, S. A., Albino do Couto, I., Bado, P., Houzel, J. C., De Miranda, J., de Freitas, M. S., Ferreira, S. T. and Panizzutti, R. (2011), Protein kinase C activity regulates d-serine availability in the brain. Journal of Neurochemistry, 116: 281–290. doi: 10.1111/j.1471-4159.2010.07102.x
- Issue published online: 16 DEC 2010
- Article first published online: 16 DEC 2010
- Accepted manuscript online: 10 NOV 2010 12:53PM EST
- Received July 20, 2010; revised manuscript received October 12, 2010; accepted October 29, 2010.
- NMDAR function;
- protein kinase C;
- serine racemase
J. Neurochem. (2011) 116, 281–290.
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.