DISC1和PDE4B是精神分裂症中相互作用的遗传因素，可调节环磷酸腺苷（cAMP）信号传导。
DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling.
作者信息
Millar J Kirsty, Pickard Benjamin S, Mackie Shaun, James Rachel, Christie Sheila, Buchanan Sebastienne R, Malloy M Pat, Chubb Jennifer E, Huston Elaine, Baillie George S, Thomson Pippa A, Hill Elaine V, Brandon Nicholas J, Rain Jean-Christophe, Camargo L Miguel, Whiting Paul J, Houslay Miles D, Blackwood Douglas H R, Muir Walter J, Porteous David J
机构信息
Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh EH4 2XU, UK.
出版信息
Science. 2005 Nov 18;310(5751):1187-91. doi: 10.1126/science.1112915.
The disrupted in schizophrenia 1 (DISC1) gene is a candidate susceptibility factor for schizophrenia, but its mechanistic role in the disorder is unknown. Here we report that the gene encoding phosphodiesterase 4B (PDE4B) is disrupted by a balanced translocation in a subject diagnosed with schizophrenia and a relative with chronic psychiatric illness. The PDEs inactivate adenosine 3',5'-monophosphate (cAMP), a second messenger implicated in learning, memory, and mood. We show that DISC1 interacts with the UCR2 domain of PDE4B and that elevation of cellular cAMP leads to dissociation of PDE4B from DISC1 and an increase in PDE4B activity. We propose a mechanistic model whereby DISC1 sequesters PDE4B in resting cells and releases it in an activated state in response to elevated cAMP.
精神分裂症相关基因1（DISC1）是精神分裂症的一个候选易感因素，但其在该疾病中的作用机制尚不清楚。在此我们报告，在一名被诊断为精神分裂症的患者以及一名患有慢性精神疾病的亲属中，编码磷酸二酯酶4B（PDE4B）的基因因平衡易位而被破坏。磷酸二酯酶可使3',5'-环磷酸腺苷（cAMP）失活，cAMP是一种与学习、记忆和情绪有关的第二信使。我们发现DISC1与PDE4B的UCR2结构域相互作用，并且细胞内cAMP水平升高会导致PDE4B与DISC1解离，PDE4B活性增加。我们提出了一种机制模型，即DISC1在静息细胞中隔离PDE4B，并在cAMP升高时以激活状态释放它。
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