Modulation of D-serine levels in brains of mice lacking PICK1.
BACKGROUND
D-serine is an endogenous coagonist of the N-methyl-D-aspartate subtype glutamate receptor. Genetic association studies have implicated genes coding for enzymes associated with D-serine metabolism in schizophrenia and bipolar disorder.


METHODS
Protein expression of serine racemase (SR) and its binding partner, protein interacting with C-kinase (PICK1), were examined by Western blotting in brains from wildtype and PICK1 knockout mice. Levels of D-serine in wildtype and PICK1 mice were also examined by an established high-pressure liquid chromatography protocol.


RESULTS
Expression of SR and PICK1 proteins was developmentally regulated. Although no change was observed in the level of SR protein, levels of D-serine were selectively decreased in the forebrain of neonatal PICK1 knockout mice, compared with those in wildtype mice.


CONCLUSIONS
PICK1 may be involved in the regulation of brain D-serine levels and SR in a spatially and temporally specific manner.
Hikida
Takatoshi
T
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Mustafa
Asif K
AK
Maeda
Kazuhisa
K
Fujii
Kumiko
K
Barrow
Roxanne K
RK
Saleh
Masoumeh
M
Huganir
Richard L
RL
Snyder
Solomon H
SH
Hashimoto
Kenji
K
Sawa
Akira
A
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency*; D019998:Racemases and Epimerases / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D000099300:Serine Racemase
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D019998:Racemases and Epimerases; D012694:Serine; D000099300:Serine Racemase; C091822:Prkcabp protein, mouse