Requirement of the tumour suppressor APC for the clustering of PSD-95 and AMPA receptors in hippocampal neurons
Requirement of the tumour suppressor APC for the clustering of PSD-95 and AMPA receptors in hippocampal neurons
复制标题
DOI：
10.1111/j.1460-9568.2007.05723.x
复制
发表时间：
2007-08-01
影响因子：
3.4
通讯作者：
Senda, Takao
中科院分区：
文献类型：
--
作者：
Shimomura, Atsushi;Ohkuma, Mahito;Senda, Takao
大肠腺瘤性息肉病（APC）基因突变与家族性腺瘤性息肉病和散发性结直肠肿瘤有关。APC基因在各种组织中普遍表达，特别是在大肠和中枢神经系统（CNS）中。在中枢神经系统中，APC蛋白的表达在胚胎和出生后早期发育期间最高。APC通过其c端区域与突触后密度(PSD)-95相关联，PSD -95是一种参与突触发育的神经元蛋白。在这里，我们研究了APC在突触发生中的作用。在培养的海马神经元中，破坏APC-PSD-95相互作用的优势负构体的过表达和使用小干扰RNA （siRNA）敲低APC的表达均抑制PSD-95和谷氨酸受体亚基的聚集，并降低α -氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）诱导的AMPA受体活性；然而，n -甲基- d -天冬氨酸（NMDA）受体亚基的聚类不受影响。这些结果提示APC参与了谷氨酸突触的发育。
Mutations in the adenomatous polyposis coli (APC) gene are associated with familial adenomatous polyposis and sporadic colorectal tumours. The APC gene is expressed ubiquitously in various tissues, especially throughout the large intestine and central nervous system (CNS). In the CNS, the expression of the APC protein is highest during embryonic and early postnatal development. APC associates through its C-terminal region with postsynaptic density (PSD)-95, a neuronal protein that participates in synapse development. Here, we examined the involvement of APC in synaptogenesis. In cultured hippocampal neurons, both overexpression of a dominant-negative construct that disrupts the APC-PSD-95 interaction and knockdown of APC expression using small interfering RNA (siRNA) inhibited the clustering of PSD-95 and a glutamate receptor subunit, and reduced alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA)-induced activity of AMPA receptors; however, the clustering of an N-methyl-D-aspartate (NMDA) receptor subunit was unaffected. These results are suggestive of APC involvement in the development of glutamatergic synapses.