ErbB receptor dimerization, localization, and co-localization in mouse lung type II epithelial cells.
ErbB receptor dimerization, localization, and co-localization in mouse lung type II epithelial cells.
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小鼠肺 II 型上皮细胞中 ErbB 受体二聚化、定位和共定位。
DOI：
10.1002/ppul.20518
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发表时间：
2006
影响因子：
3.1
通讯作者：
Dammann,ChristianeEL
中科院分区：
文献类型：
--
作者：
Zscheppang,Katja;Korenbaum,Elena;Bueter,Wolfgang;Ramadurai,SujathaM;Nielsen,HeberC;Dammann,ChristianeEL
ErbB受体对胚胎神经元和心脏发育至关重要。ErbB受体配体神经调节蛋白（NRG）和表皮生长因子（EGF）在发育中的肺，特别是在间充质诱导的胎儿表面活性剂合成的II型上皮细胞中发挥重要作用。不同的erbB受体配体通过刺激特异性erbB-二聚体引起不同的生物学效应。目前尚不清楚erbB二聚体的二聚化、细胞定位和共定位在II型上皮细胞中是如何调节的。我们假设erbB受体在II型细胞中具有独特的二聚化、定位和共定位模式。在表达所有四种erbB受体的小鼠II型上皮细胞中，erbB 1和erbB 4是优选的二聚化伴侣。这些二聚化模式是配体独立的。共聚焦显微镜显示这些跨膜受体具有很强的核定位。在未受刺激的细胞中，erbB 1和erbB 2主要定位于细胞核，而细胞质的强度较低。而erbB 1主要分布于核仁区，erbB 2则不分布于核仁区。ErbB 3仅定位于核仁。ErbB 4弥散分布于细胞核和细胞质中，与ErbB 2一样，不分布于核仁区。EGF或NRG的短期刺激导致erbB 1，erbB 2和erbB 4的更明显的核染色。所有四种受体在刺激后彼此共定位，但强度不同。两种已知的胎儿表面活性物质合成刺激剂，NRG和含NRG的成纤维细胞条件培养基，以不同的方式改变了二聚化伴侣erbB 4和erbB 2的细胞定位。我们得出结论，erbB受体在II型上皮细胞中具有受体特异性定位和二聚化模式。小儿肺醇。2006; 41：1205-1212.© 2006 Wiley利斯公司
ErbB receptors are crucial for embryonic neuronal and cardiac development. ErbB receptor ligands neuregulin (NRG) and epidermal growth factor (EGF) play a major role in the developing lung, specifically in mesenchymal induced fetal surfactant synthesis by type II epithelial cells. Different erbB receptor ligands cause diverse biologic effects by stimulating specific erbB‐dimers. It is not known how dimerization, cellular localization, and co‐localization of erbB dimers are regulated in type II epithelial cells. We hypothesized that erbB receptors have a distinct dimerization, localization, and co‐localization pattern in type II cells. In mouse type II epithelial cells, which express all four erbB receptors, erbB1 and erbB4 were the preferred dimerization partners. These dimerization patterns were ligand independent. Confocal microscopy showed these transmembrane receptors exhibited a strong nuclear localization. In non‐stimulated cells, both erbB1 and erbB2 were predominantly localized to the nucleus and less intensely to the cytoplasm. However, erbB1 was mainly found in the nucleoli, whereas erbB2 spared the nucleolar region. ErbB3 was exclusively located in the nucleoli. ErbB4 was diffusely located in nucleus and cytoplasm, and like erbB2 spared the nucleolar region. Short stimulation with either EGF or NRG led to a more pronounced nuclear staining for erbB1, erbB2, and erbB4. All four receptors co‐localized with each other after stimulation, but with varying intensity. The two known stimulators of fetal surfactant synthesis, NRG and NRG‐containing fibroblast conditioned medium, changed cellular localization of the dimerization partners erbB4 and erbB2 in a distinct fashion. We conclude that erbB receptors have a receptor‐specific localization and dimerization pattern in type II epithelial cells. Pediatr Pulmonol. 2006; 41:1205–1212. © 2006 Wiley‐Liss, Inc.