Protein kinase C activity regulates D-serine availability in the brain.

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.

journal_name

J Neurochem

authors

Vargas-Lopes C,Madeira C,Kahn SA,Albino do Couto I,Bado P,Houzel JC,De Miranda J,de Freitas MS,Ferreira ST,Panizzutti R

doi

10.1111/j.1471-4159.2010.07102.x

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

281-90

issue

2

eissn

0022-3042

issn

1471-4159

journal_volume

116

pub_type

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