Serine racemase binds to PICK1: potential relevance to schizophrenia
Serine racemase binds to PICK1: potential relevance to schizophrenia
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DOI：
10.1038/sj.mp.4001776
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发表时间：
2006-02-01
影响因子：
11
通讯作者：
Sawa, A
中科院分区：
文献类型：
--
作者：
Fujii, K;Maeda, K;Sawa, A
从遗传和临床药理学研究中积累的证据表明，D-丝氨酸，一种内源性的NMDA亚型谷氨酸受体的凝血剂，可能与精神分裂症（SZ）有关。虽然已经报道了D-丝氨酸降解基因的关联，例如D-氨基酸氧化酶和G72，但D-丝氨酸在SZ中的作用尚不清楚。在这项研究中，我们确定和表征蛋白质相互作用与C-激酶（PICK 1）作为蛋白质相互作用的D-丝氨酸合成酶，丝氨酸消旋酶（SR）。内源性PICK 1和SR的结合需要PICK 1的PDZ结构域。编码PICK 1的基因位于染色体22 q13，这是一个经常与SZ连锁的区域。在一项病例对照关联研究中，使用了特征良好的日本受试者，我们观察到PICK 1基因与SZ的关联，这在混乱的SZ中更为突出。我们的研究结果暗示PICK 1作为SZ的易感基因与D-丝氨酸在疾病中的作用一致。
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.