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Serine racemase binds to PICK1: potential relevance to schizophrenia

Molecular Psychiatry volume 11, pages 150–157 (2006)Cite this article

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.

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Acknowledgements

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.

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Author notes

  1. K Fujii and K Maeda: These authors contributed equally to the work.

  2. T Hikida, A K Mustafa and R Balkissoon: These authors contributed equally to the work.

Authors and Affiliations

  1. Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    K Fujii, K Maeda, R Balkissoon, Y Ozeki, S H Snyder & A Sawa

  2. Department of Psychiatry, Shiga University of Medical Science, Shiga, Japan

    K Fujii, Y Ozeki, M Okawa & R L Huganir

  3. Division of Neuropsychiatry, Faculty of Medicine, Tottori University, Yonago, Japan

    K Maeda, T Yamada & R Kawahara

  4. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    T Hikida, A K Mustafa, J Xia, S H Snyder & A Sawa

  5. Program in Cellular Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    R L Huganir, S H Snyder & A Sawa

  6. Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan

    H Ujike

  7. Department of Pharmacology and Molecular Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    S H Snyder

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  1. K Fujii
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Fujii, K., Maeda, K., Hikida, T. et al. Serine racemase binds to PICK1: potential relevance to schizophrenia. Mol Psychiatry 11, 150–157 (2006). https://doi.org/10.1038/sj.mp.4001776

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