Widespread expression of ErbB2, ErbB3 and ErbB4 in non-human primate brain
Widespread expression of ErbB2, ErbB3 and ErbB4 in non-human primate brain
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DOI：
10.1016/j.brainres.2006.11.047
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发表时间：
2007-03-30
期刊：
影响因子：
2.9
通讯作者：
Weickert, Cynthia Shannon
中科院分区：
文献类型：
--
作者：
Thompson, Mia;Lauderdale, Simone;Weickert, Cynthia Shannon
神经调节蛋白（NRG）信号蛋白与ErbB受体相互作用，导致发育中的大脑神经元和胶质细胞的增殖、分化和迁移。NRG-1/ErbB4是精神分裂症的易感基因，但对灵长类动物中ErbB受体的神经解剖学表达知之甚少。通过原位杂交，我们发现ErbB2、ErbB3和ErbB4受体mRNA在幼猴和成年猴的端脑中广泛表达，其中ErbB2和ErbB4 mRNA比ErbB3 mRNA更丰富。与白质相比，ErbB2和ErbB4 mRNA在灰质中的表达水平较高，而ErbB3 mRNA在灰质和白质中的表达水平均较低。我们还用免疫印迹和免疫组织化学方法表征了ErbB蛋白的表达。在额叶皮层，ErbB2、ErbB3和ErbB4抗体免疫染色神经元体细胞和细胞核。ErbB2抗体也对脑脊液表面的胶质细胞进行免疫染色。在白质内，ErbB3和ErbB4蛋白定位于假定的间质白质神经元，而ErbB2蛋白则在胶质细胞中发现。Western blotting显示每个ErbB的免疫阳性条带在180-200 kDa之间，这与全长ErbB的大小一致。在全脑匀浆和单独的细胞质和核提取物中，每个ErbB受体也被鉴定出较小的免疫阳性带，这表明核ErbB在大脑中具有反向信号传导能力。ErbB受体的普遍表达表明，在幼年和成年灵长类动物的大脑中，许多细胞群都有可能以各种方式对NRG-1作出反应。(c) 2006 Elsevier B.V.版权所有
Neuregulin (NRG) signaling proteins interact with ErbB receptors leading to the proliferation, differentiation and migration of neurons and glia in the developing brain. NRG-1/ErbB4 are susceptibility genes for schizophrenia, yet little is known about the neuroanatomical expression of ErbB receptors specifically in primates. We find widespread expression of ErbB2, ErbB3 and ErbB4 receptor mRNAs throughout the telencephalon of juvenile and adult monkeys with in situ hybridization, with ErbB2 and ErbB4 mRNA more abundant than ErbB3 mRNA. ErbB2 and ErbB4 mRNA are expressed at higher levels in grey matter compared to white matter, whereas ErbB3 mRNA is expressed at low levels in both grey and white matter. We also characterized ErbB protein expression with immunoblotting and immunohistochemistry. In frontal cortex, ErbB2, ErbB3 and ErbB4 antibodies immunostained neuronal soma and nuclei. The ErbB2 antibody also immunostained glia at the pial surface. Within white matter, ErbB3 and ErbB4 proteins were localized to putative interstitial white matter neurons while ErbB2 protein was found in glia. Western blotting revealed immunopositive bands at similar to 180-200 kDa for each ErbB, which is consistent with the size of full-length ErbBs. Smaller immunopositive bands were also identified for each ErbB receptor in whole brain homogenates and separate cytoplasmic and nuclear extracts suggesting nuclear ErbB-back-signaling capacity in the brain. The ubiquitous expression of ErbB receptors indicates that many cell populations throughout the brain of juvenile and adult primates have the potential to respond to NRG-1 in a variety of ways. (c) 2006 Elsevier B.V. All rights reserved.