Neuronal localization of the Adenomatous polyposis coli tumor suppressor protein
Neuronal localization of the Adenomatous polyposis coli tumor suppressor protein
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DOI：
10.1016/s0306-4522(98)00605-8
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发表时间：
1999-01-01
期刊：
影响因子：
3.3
通讯作者：
Baraban, JM
中科院分区：
文献类型：
--
作者：
Brakeman, JSF;Gu, SH;Baraban, JM
最近的生化研究表明，大肠腺瘤性息肉病基因在大脑中高水平表达，该基因最初是通过与结肠癌的联系而被发现的。此外，这种肿瘤抑制蛋白结合disc - large和β -连环蛋白（与组织突触结构有关的蛋白质）的能力表明APC在神经元信号传导中的作用。然而，关于其在脑中的定位，解剖学研究提供了相互矛盾的结果。原位杂交研究预测APC的神经元表达，而用一组n端抗体进行的免疫染色研究检测到胶质细胞，特别是少突胶质细胞的染色。在这项研究中，我们研究了这种差异的基础，并提供证据表明，在以前的研究中检测到的胶质染色模式反映了与不相关抗原的交叉反应性，而不是APC的定位。此外，我们用c端APC抗体进行了免疫组织化学研究，结果显示神经元的染色模式与原位研究预测的密切匹配。例如，在海马锥体神经元和齿状颗粒细胞中检测到APC免疫染色，这与APC mRNA的定位非常吻合。其他区域APC免疫染色显示，大的神经元，包括V层皮质锥体神经元、小脑浦肯野细胞和嗅球二尖瓣细胞，显示出特别强烈的染色。在标记的神经元中，细胞质以及树突和轴突中可见APC染色。为了明确APC在脑中的定位，我们进行了额外的原位杂交和免疫组织化学研究。这些结果提供了令人信服的证据，证明APC主要在神经元中表达，而不是像以前报道的那样在神经胶质细胞中表达。(c) 1999年ibro。Elsevier Science Ltd.出版。
Recent biochemical studies have demonstrated that the adenomatous polyposis coli gene, initially identified via its link to colon cancer, is expressed at high levels in the brain. Furthermore, the ability of this tumor suppressor protein to bind to Discs-Large and beta-catenin, proteins implicated in organizing synaptic structure, point to a role for APC in neuronal signalling. However, anatomical studies have provided conflicting results regarding its localization in brain. In situ hybridization studies predict neuronal expression of APC, while immunostaining studies performed with a panel of N-terminal antibodies detected staining of glial cells, especially oligodendrocytes. In this study, we have examined the basis for this discrepancy and provide evidence that the glial staining pattern detected in previous studies reflects cross-reactivity with an unrelated antigen rather than the localization of APC. Furthermore, we have performed immunohistochemical studies with a C-terminal APC antibody which reveal a neuronal pattern of staining closely matching that predicted by the in situ studies. For example, in the hippocampus APC immunostaining is detected in the pyramidal neurons and dentate granule cells, which fits well with the localization of APC mRNA. Examination of APC immunostaining in other regions revealed that particularly intense staining was displayed by large neurons, including layer V cortical pyramidal neurons, cerebellar Purkinje cells, and olfactory bulb mitral cells. Within labeled neurons, APC staining was apparent in the cytoplasm, as well as in dendritic and axonal processes.To help clarify the localization of APC in brain, we have conducted additional in situ hybridization and immunohistochemical studies. These results provide compelling evidence that APC is expressed predominantly in neurons rather than in glial cells as reported previously. (C) 1999 IBRO. Published by Elsevier Science Ltd.