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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)150-157
Number of pages8
JournalMolecular psychiatry
Volume11
Issue number2
DOIs
StatePublished - Feb 2006

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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  • Cite this

    Fujii, K., Maeda, K., Hikida, T., Mustafa, A. K., Balkissoon, R., Xia, J., Yamada, T., Ozeki, Y., Kawahara, R., Okawa, M., Huganir, R. L., Ujike, H., Snyder, S. H., & Sawa, A. (2006). Serine racemase binds to PICK1: Potential relevance to schizophrenia. Molecular psychiatry, 11(2), 150-157. https://doi.org/10.1038/sj.mp.4001776