DISC1, PDE4B, and NDE1 at the centrosome and synapse
DISC1, PDE4B, and NDE1 at the centrosome and synapse
复制标题
DOI：
10.1016/j.bbrc.2008.10.120
复制
发表时间：
2008-12-26
影响因子：
3.1
通讯作者：
Millar, J. Kirsty
中科院分区：
文献类型：
--
作者：
Bradshaw, Nicholas J.;Ogawa, Fumiaki;Millar, J. Kirsty
精神分裂症1(DISC1)是精神分裂症和其他主要精神疾病的危险因素。它的蛋白结合伙伴包括核分布因子E同源物(NDE1和NDEL1)、Lis1以及磷酸二酯酶4B和4D(PDE4B和PDE4D)。我们证明了NDE1、NDEL1和LIS1以及它们的结合伙伴dynein在细胞内与DISC1、PDE4B和PDE4D结合，并提供了这种复合体存在于中心体的证据。Lis1和NDEL1以前被认为是突触的，现在我们证明了DISC1、NDE1和PDE4B在培养神经元的突触中的定位。NDE1被cAMP依赖的蛋白激酶A(PKA)磷酸化，而PKA的活性又受包括PDE4在内的磷酸二酯酶的cAMP水解酶活性的调节。我们认为DISCI作为所有这些蛋白质的组装支架，NDE1/NDEL1/Lis1/dynein复合体通过PKA和PDE4受到cAMP水平的调节。(C)2008 Elsevier Inc.保留所有权利。
Disrupted-In-Schizophrenia 1 (DISC1) is a risk factor for schizophrenia and other major mental illnesses. Its protein binding partners include the Nuclear Distribution Factor E Homologs (NDE1 and NDEL1), LIS1, and phosphodiesterases 4B and 4D (PDE4B and PDE4D). We demonstrate that NDE1, NDEL1 and LIS1, together with their binding partner dynein, associate with DISC1, PDE4B and PDE4D within the cell, and provide evidence that this complex is present at the centrosome. LIS1 and NDEL1 have been previously Suggested to be synaptic, and we now demonstrate localisation of DISC1, NDE1, and PDE4B at synapses in Cultured neurons. NDE1 is phosphorylated by cAMP-dependant Protein Kinase A (PKA), whose activity is, in turn, regulated by the cAMP hydrolysis activity of phosphodiesterases, including PDE4. We propose that DISCI acts as an assembly scaffold for all of these proteins and that the NDE1/NDEL1/LIS1/dynein complex is modulated by cAMP levels via PKA and PDE4. (C) 2008 Elsevier Inc. All rights reserved.