ErbB transmembrane tyrosine kinase receptors are differentially expressed throughout the adult rat central nervous system

ErbB transmembrane tyrosine kinase receptors are differentially expressed throughout the adult rat central nervous system
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DOI:
10.1002/cne.1127
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发表时间:
2001-04-23
影响因子:
2.5
通讯作者:
Carroll, SL
Carroll, SL
中科院分区:
医学3区
文献类型:
--
作者:
Gerecke, KM;Wyss, JM;Carroll, SL

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神经调节蛋白(NRG)家族的生长和分化因子及其erbB受体对神经系统的发育起重要作用,但它们在成人大脑中的分布和功能尚不清楚。本研究表明,erbB2、erbB3和erbB4转录本和蛋白分布于成年大鼠的所有区域;大脑。这三种受体在神经元和神经胶质中表达不同。一些神经元只表达erbB激酶的一个子集,而另一些神经元表达所有三种erbB受体,但将这些多肽隔离在不同的细胞室中。在突触丰富的区域,erbB免疫反应表现为点状、轴突和/或树突相关染色,表明NRGs参与了成人大脑突触的形成和维持。在一些神经元中也存在ErbB标记,表明NRGs在突触之外的位点起作用。成人脑胶质细胞中erbB3和erbB4的表达也存在差异。白质中大约一半的erbB3标记与S100 β +/胶质纤维酸性蛋白阴性大胶质细胞(即少突胶质细胞或胶质纤维酸性蛋白阴性星形胶质细胞)相关。相比之下,灰质大胶质细胞不表达erbBS。白质中剩余的erbBS免疫反应性和erbB3胶质染色似乎与小胶质细胞有关。这些结果表明,erbB受体在成年大鼠脑中表达广泛,且各erbB受体亚型分布明显。erbB受体在神经元和胶质细胞中的不同分布以及这些激酶之间已知的功能差异表明NRGs对这些细胞有不同的作用。NRGs及其erbB受体在成熟大脑中的持续表达也表明这些分子在整个生命过程中在大脑中发挥重要作用。(C) 2001 Wiley-Liss, Inc。
The neuregulin (NRG) family of growth and differentiation factors and their erbB receptors contribute importantly to the development of the nervous system, but their distribution and function in the adult brain are poorly understood. The present study showed that erbB2, erbB3, and erbB4, transcripts and protein are distributed throughout all areas of adult rat; brain. These three receptors were differentially expressed in neurons and glia. Some neurons expressed only a subset of erbB kinases, whereas other neurons expressed all three erbB receptors but sequestered each of these polypeptides into distinct cellular compartments. In synapse-rich regions, erbB immunoreactivity appeared as punctate-, axon-, and/or dendrite-associated staining, suggesting that NRGs are involved in the formation and maintenance of synapses in adult brain. ErbB labeling also was present in neuronal some, indicating that NRGs act at sites in addition to the synapse. Glia in adult brain also differentially expressed erbB3 and erbB4. Approximately half of the erbB3 labeling in white matter was associated with S100 beta+/glial fibrillary acidic protein negative macroglia (i.e., oligodendrocytes or glial fibrillary acidic protein negative astrocytes). In contrast, macroglia in gray matter did not express erbBS. The remaining erbBS immunoreactivity in white matter and erbB3 glial staining seemed to be associated with microglia. These results showed that erbB receptors are expressed widely in adult rat brain and that each erbB receptor subtype has a distinct distribution. The differential distributions of erbB receptors in neurons and glia and the known functional differences between these kinases suggest that NRGs have distinct effects on these cells. The continued expression of NRGs and their erbB receptors in mature brain also implies that these molecules perform important functions in the brain throughout life. (C) 2001 Wiley-Liss, Inc.