Modulation of epithelial morphology, monolayer permeability, and cell migration by growth arrest specific 3/peripheral myelin protein 22
Modulation of epithelial morphology, monolayer permeability, and cell migration by growth arrest specific 3/peripheral myelin protein 22
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DOI：
10.1091/mbc.e04-07-0551
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发表时间：
2005-03-01
影响因子：
3.3
通讯作者：
Notterpek, L
中科院分区：
文献类型：
--
作者：
Roux, KJ;Amici, SA;Notterpek, L
外周髓鞘蛋白22(PMP22)与遗传性周围神经病有关。尽管PMP22主要被认为是周围神经髓鞘的跨膜成分，但它定位于上皮细胞和内皮细胞-细胞连接，其功能尚不清楚。在这份报告中，我们研究了PMP22在上皮生物学中的作用。人PMP22(HPMP22)的表达减缓了MDCK细胞的生长，并诱导MDCK细胞形态扁平。HPMP22的表达增加了MDCK单层的跨上皮电阻值(TER)和细胞旁流量。钙离子转换后，与PMP22的第二个而非第一个胞外环相对应的多肽干扰了TER和细胞旁流量的恢复。最后，在创伤后，表达hPMP22的上皮单层不能正常迁移。这些结果表明，PMP22能够调节上皮细胞生物学的几个方面，包括连接通透性和伤口闭合。
Peripheral myelin protein 22 (PMP22) is associated with a subset of hereditary peripheral neuropathies. Although predominantly recognized as a transmembrane constituent of peripheral nerve myelin, PMP22 is localized to epithelial and endothelial cell-cell junctions, where its function remains unknown. In this report, we investigated the role of PMP22 in epithelial biology. Expression of human PMP22 (hPMP22) slows cell growth and induces a flattened morphology in Madin-Darby canine kidney (MDCK) cells. The transepithelial electrical resistance (TER) and paracellular flux of MDCK monolayers are elevated by hPMP22 expression. After calcium switch, peptides corresponding to the second, but not the first, extracellular loop of PMP22 perturb the recovery of TER and paracellular flux. Finally, subsequent to wounding, epithelial monolayers expressing hPMP22 fail to migrate normally. These results indicate that PMP22 is capable of modulating several aspects of epithelial cell biology, including junctional permeability and wound closure.