Serine racemase binds to PICK1: potential relevance to schizophrenia.
Accumulating evidence from both genetic and clinico-pharmacological studies suggests that D-serine, an endogenous coagonist to the NMDA subtype glutamate receptor, may be implicated in schizophrenia (SZ). Although an association of genes for D-serine degradation, such as D-amino acid oxidase and G72, has been reported, a role for D-serine in SZ has been unclear. In this study, we identify and characterize protein interacting with C-kinase (PICK1) as a protein interactor of the D-serine synthesizing enzyme, serine racemase (SR). The binding of endogenous PICK1 and SR requires the PDZ domain of PICK1. The gene coding for PICK1 is located at chromosome 22q13, a region frequently linked to SZ. In a case-control association study using well-characterized Japanese subjects, we observe an association of the PICK1 gene with SZ, which is more prominent in disorganized SZ. Our findings implicating PICK1 as a susceptibility gene for SZ are consistent with a role for D-serine in the disease.
Fujii
K
K
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Maeda
K
K
Hikida
T
T
Mustafa
A K
AK
Balkissoon
R
R
Xia
J
J
Yamada
T
T
Ozeki
Y
Y
Kawahara
R
R
Okawa
M
M
Huganir
R L
RL
Ujike
H
H
Snyder
S H
SH
Sawa
A
A
D000328:Adult; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D019998:Racemases and Epimerases / Q000378:metabolism*; D012559:Schizophrenia / Q000145:classification / Q000201:enzymology* / Q000235:genetics*; D012694:Serine / Q000096:biosynthesis / Q000378:metabolism*; D000099300:Serine Racemase
D002352:Carrier Proteins; D009687:Nuclear Proteins; D019998:Racemases and Epimerases; D012694:Serine; D000099300:Serine Racemase; C498297:PICk1 protein, human