Disrupted in schizophrenia 1 interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia
Disrupted in schizophrenia 1 interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia
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DOI：
10.1038/sj.mp.4001880
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发表时间：
2007-01-01
影响因子：
11
通讯作者：
Brandon, N. J.
中科院分区：
文献类型：
--
作者：
Camargo, L. M.;Collura, V.;Brandon, N. J.
Disrupted in Schizophrenia 1（DISC 1）是一个与精神分裂症患者和正常老年人群的认知缺陷相关的精神分裂症风险基因。在这项研究中，我们在DISC 1周围生成了一个蛋白质-蛋白质相互作用（PPI）网络。这已经通过利用迭代酵母双杂交（Y2 H）筛选，结合详细的途径和功能分析实现。这个所谓的“DISC 1相互作用组”包含许多新的PPI，并提供了一个分子框架，以探索DISC 1的功能。该网络涉及DISC 1在细胞骨架的稳定性和组织，细胞内运输和细胞周期/分裂的过程。特别是，DISC 1看起来具有与必需突触蛋白一致的PPI谱，这与在突触水平观察到的潜在分子病理学和精神分裂症患者行为上观察到的认知缺陷非常吻合。利用类似的方法与dysbindin（DTNBP 1），第二个精神分裂症的风险基因，我们表明，dysbindin和DISC 1共享共同的PPI，这表明他们可能会影响共同的生物过程，精神分裂症风险基因的功能可能会收敛。
Disrupted in Schizophrenia 1 (DISC1) is a schizophrenia risk gene associated with cognitive deficits in both schizophrenics and the normal ageing population. In this study, we have generated a network of protein-protein interactions ( PPIs) around DISC1. This has been achieved by utilising iterative yeast-two hybrid (Y2H) screens, combined with detailed pathway and functional analysis. This so-called 'DISC1 interactome' contains many novel PPIs and provides a molecular framework to explore the function of DISC1. The network implicates DISC1 in processes of cytoskeletal stability and organisation, intracellular transport and cell-cycle/division. In particular, DISC1 looks to have a PPI profile consistent with that of an essential synaptic protein, which fits well with the underlying molecular pathology observed at the synaptic level and the cognitive deficits seen behaviourally in schizophrenics. Utilising a similar approach with dysbindin (DTNBP1), a second schizophrenia risk gene, we show that dysbindin and DISC1 share common PPIs suggesting they may affect common biological processes and that the function of schizophrenia risk genes may converge.