Differential regulation of junctional complex assembly in renal epithelial cell lines
Differential regulation of junctional complex assembly in renal epithelial cell lines
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DOI：
10.1152/ajpcell.00583.2002
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发表时间：
2003-07-01
影响因子：
5.5
通讯作者：
Marrs, JA
中科院分区：
文献类型：
--
作者：
Gopalakrishnan, S;Hallett, MA;Marrs, JA
调节紧密连接和粘附连接组装的几个信号通路被表征。Calpeptin通过抑制SH2-containing phosphatase-2 （SHP-2）激活Rho-GTPase信号传导，激活成纤维细胞中的应激纤维组装。在这里，我们研究了calpeptin对Madin-Darby犬肾（MDCK）和LLC-PK上皮细胞中应激纤维和连接复合物组装的影响。Calpeptin诱导MDCK细胞应力纤维的断裂和Rho GTPase活性的抑制。有趣的是，calpeptin增强了LLC-PK上皮细胞中应激纤维的形成。Calpeptin处理MDCK细胞导致细胞间连接处的occluden -1 （ZO-1）和occludin移位，以及ZO-1和ZO-2上磷酸酪氨酸的损失，但对紧密连接处的通透性没有任何可检测到的影响。令人惊讶的是，calpeptin增加了LLC-PK细胞的细胞旁通透性，尽管它不影响紧密连接的组装。Calpeptin在MDCK细胞中也能调节粘附体的连接组装，但在LLC-PK细胞中没有。Calpeptin处理MDCK细胞诱导E-cadherin和β -catenin从细胞间连接处重新分布，并降低p120ctn与E-cadherin/catenin复合物的关联。总之，我们的研究表明，calpeptin在MDCK和LLC-PK上皮细胞中对应激纤维和连接复合体的组装有差异调节，表明这些途径可能以细胞系特异性的方式进行调节。
Several signaling pathways that regulate tight junction and adherens junction assembly are being characterized. Calpeptin activates stress fiber assembly in fibroblasts by inhibiting SH2-containing phosphatase-2 (SHP-2), thereby activating Rho-GTPase signaling. Here, we have examined the effects of calpeptin on stress fiber and junctional complex assembly in Madin-Darby canine kidney (MDCK) and LLC-PK epithelial cells. Calpeptin induced disassembly of stress fibers and inhibition of Rho GTPase activity in MDCK cells. Interestingly, calpeptin augmented stress fiber formation in LLC-PK epithelial cells. Calpeptin treatment of MDCK cells resulted in a displacement of zonula occludens-1 (ZO-1) and occludin from cell-cell junctions and a loss of phosphotyrosine on ZO-1 and ZO-2, without any detectable effect on tight junction permeability. Surprisingly, calpeptin increased paracellular permeability in LLC-PK cells even though it did not affect tight junction assembly. Calpeptin also modulated adherens junction assembly in MDCK cells but not in LLC-PK cells. Calpeptin treatment of MDCK cells induced redistribution of E-cadherin and beta-catenin from intercellular junctions and reduced the association of p120ctn with the E-cadherin/catenin complex. Together, our studies demonstrate that calpeptin differentially regulates stress fiber and junctional complex assembly in MDCK and LLC-PK epithelial cells, indicating that these pathways may be regulated in a cell line-specific manner.