Serine racemase binds to PICK1: potential relevance to schizophrenia

Mol Psychiatry. 2006 Feb;11(2):150-7. doi: 10.1038/sj.mp.4001776.

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.

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Astrocytes / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Polymorphism, Single Nucleotide
  • Racemases and Epimerases / metabolism*
  • Schizophrenia / classification
  • Schizophrenia / enzymology*
  • Schizophrenia / genetics*
  • Serine / biosynthesis
  • Serine / metabolism*

Substances

  • Carrier Proteins
  • Nuclear Proteins
  • PICk1 protein, human
  • Serine
  • Racemases and Epimerases
  • serine racemase