Serine racemase binds to PICK1: Potential relevance to schizophrenia

K. Fujii; K. Maeda; T. Hikida; A. K. Mustafa; R. Balkissoon; J. Xia; T. Yamada; Y. Ozeki; R. Kawahara; M. Okawa; R. L. Huganir; H. Ujike; S. H. Snyder; A. Sawa

doi:10.1038/sj.mp.4001776

Serine racemase binds to PICK1: Potential relevance to schizophrenia

K. Fujii, K. Maeda, T. Hikida, A. K. Mustafa, R. Balkissoon, J. Xia, T. Yamada, Y. Ozeki, R. Kawahara, M. Okawa, R. L. Huganir, H. Ujike, S. H. Snyder, A. Sawa

School of Medicine

Research output: Contribution to journal › Article › peer-review

102 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	150-157
Number of pages	8
Journal	Molecular psychiatry
Volume	11
Issue number	2
DOIs	https://doi.org/10.1038/sj.mp.4001776
State	Published - Feb 2006

Keywords

Case-control study
D-serine
PICK1
Schizophrenia
Serine racemase
Yeast two-hybrid

ASJC Scopus subject areas

Psychiatry and Mental health
Cellular and Molecular Neuroscience
Molecular Biology

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10.1038/sj.mp.4001776

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title = "Serine racemase binds to PICK1: Potential relevance to schizophrenia",

abstract = "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.",

keywords = "Case-control study, D-serine, PICK1, Schizophrenia, Serine racemase, Yeast two-hybrid",

author = "K. Fujii and K. Maeda and T. Hikida and Mustafa, {A. K.} and R. Balkissoon and J. Xia and T. Yamada and Y. Ozeki and R. Kawahara and M. Okawa and Huganir, {R. L.} and H. Ujike and Snyder, {S. H.} and A. Sawa",

note = "Funding Information: We thank Drs Ann Pulver, David Valle, and Peter Zandi for critical reading of the manuscript. We thank Ms Yukiko Lema for preparation of the figures. We appreciate Dr Yukihiko Shirayama, Ms Pratima Dullor and Mr John Kleiderlein for technical assistance. This work was supported by US Public Health Service Grant MH-069853, foundation grants from NARSAD, S-R and Stanley (to AS); US Public Health Service Grant MH-18501 and Research Scientist Award DA00074 (to SHS); National Institutes of Health Grant NS036715 and the Howard Hughes Medical Institutes (to RLH). TH is supported by fellowships from the Sankyo Foundation of Life Science and Uehara Memorial Foundation.",

year = "2006",

month = feb,

doi = "10.1038/sj.mp.4001776",

language = "English (US)",

volume = "11",

pages = "150--157",

journal = "Molecular psychiatry",

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T1 - Serine racemase binds to PICK1

T2 - Potential relevance to schizophrenia

AU - Fujii, K.

AU - Maeda, K.

AU - Hikida, T.

AU - Mustafa, A. K.

AU - Balkissoon, R.

AU - Xia, J.

AU - Yamada, T.

AU - Ozeki, Y.

AU - Kawahara, R.

AU - Okawa, M.

AU - Huganir, R. L.

AU - Ujike, H.

AU - Snyder, S. H.

AU - Sawa, A.

N1 - Funding Information: We thank Drs Ann Pulver, David Valle, and Peter Zandi for critical reading of the manuscript. We thank Ms Yukiko Lema for preparation of the figures. We appreciate Dr Yukihiko Shirayama, Ms Pratima Dullor and Mr John Kleiderlein for technical assistance. This work was supported by US Public Health Service Grant MH-069853, foundation grants from NARSAD, S-R and Stanley (to AS); US Public Health Service Grant MH-18501 and Research Scientist Award DA00074 (to SHS); National Institutes of Health Grant NS036715 and the Howard Hughes Medical Institutes (to RLH). TH is supported by fellowships from the Sankyo Foundation of Life Science and Uehara Memorial Foundation.

PY - 2006/2

Y1 - 2006/2

N2 - 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.

AB - 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.

KW - Case-control study

KW - D-serine

KW - PICK1

KW - Schizophrenia

KW - Serine racemase

KW - Yeast two-hybrid

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AN - SCOPUS:31544465933

SN - 1359-4184

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EP - 157

JO - Molecular psychiatry

JF - Molecular psychiatry

IS - 2

ER -

Serine racemase binds to PICK1: Potential relevance to schizophrenia

Abstract

Keywords

ASJC Scopus subject areas

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