Assocation between PICK1 gene and schizophrenia

点击翻译按钮获取中文摘要

D-serine is an endogenous cagonist of the N-methy-D-aspartate subtype of glutamate receptor. Genetic association studies have implicated genes cording for enzymes associated with D-serine metabolism in schizophrenia (SZ) and bipolar disorder. We have identified and characterized protein interacting with C-kinase (PICK1) as a protein interacter of the D-serine synthesizing enzyme, serine racemase (SR). We also have observed an association of the PICK1 gene with SZ, which is more prominent in disorganized group of SZ. In this study, we explored the role of PICK1 for D-serine synthesis in cell culture models and in vivo transfection of PICK1 into the brain of animals. Furthermore, we also explored the association between PICK1 and neuropsychological markers.First, we use HEK293 cells, which have almost no endogenous SR. In HEK293 cells transfected with wildtype PICK1, SR, or both, we observed and increased ratio of D-serine to SR in cells expressing both SR and PICK1 compared with SR alone. The SR mutant K27A/D28A, which cannot interact with each other, abolished the increase in D-serine. Reducing PICK1 expression using siRNA to PICK1 also prevented the increase in D-serine production. Next, we examined the effect of overtransfection of PICK1 for animals in vivo. We found the tendency of increasing of D-serine in the transfected region of the brains, but it was not significant. Next, we investigated the association of PICK1 polymorphisms with anitisacade eye movements in SZ patients, but we could not find significant result from our subjects. These results suggest that PICK1 may be involved in increasing D-serine levels because of its interaction with SR. Further research is needed to explore the association between PICK1 and neuropsychological markers in SZ.