Junctional adhesion molecule-A is critical for the formation of pseudocanaliculi and modulates E-cadherin expression in hepatic cells
Junctional adhesion molecule-A is critical for the formation of pseudocanaliculi and modulates E-cadherin expression in hepatic cells
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DOI：
10.1074/jbc.m703592200
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发表时间：
2007-09-21
影响因子：
4.8
通讯作者：
Duncan, Stephen A.
中科院分区：
文献类型：
--
作者：
Konopka, Genevieve;Tekiela, Jackie;Duncan, Stephen A.
肝细胞是极化的上皮细胞，其功能取决于它们区分位于细胞间紧密连接的顶面和基底面的能力。有人提出，起源于这些连接的信号级联通过控制细胞核中的基因表达来影响细胞活性。为了评估这一建议的有效性，关于肝细胞，我们耗尽表达的紧密连接蛋白连接粘附分子-A（JAM-A）的HepG 2人肝癌细胞系。JAM-A的减少导致细胞形态的显著变化，细胞形成1-2个细胞厚的片层，而不是正常的多层簇。在没有JAM-A的情况下，其他紧密连接蛋白被错误定位，并且形成肝细胞顶面的假小管因此不存在。在JAM-A水平降低的细胞中，粘附连接蛋白E-钙粘蛋白具有强烈的转录诱导作用。E-cadherin的这种增加是部分负责所观察到的细胞形态和紧密连接蛋白的错误定位的改变。因此，我们提出了一种新的机制，可以用来调节肝细胞之间的粘附紧密连接和adherens连接的特定组件之间的串扰。
Hepatocytes are polarized epithelial cells whose function depends upon their ability to distinguish between the apical and basolateral surfaces that are located at intercellular tight junctions. It has been proposed that the signaling cascades originating at these junctions influence cellular activity by controlling gene expression in the cell nucleus. To assess the validity of this proposal with regard to hepatocytes, we depleted expression of the tight junction protein junctional adhesion molecule-A (JAM-A) in the HepG2 human hepatocellular carcinoma cell line. Reduction of JAM-A resulted in a striking change in cell morphology, with cells forming sheets 1-2 cells thick instead of the normal multilayered clusters. In the absence of JAM-A, other tight junction proteins were mislocalized, and pseudo-canaliculi, which form the apical face of the hepatocyte, were consequently absent. There was a strong transcriptional induction of the adherens junction protein E-cadherin in cells with reduced levels of JAM-A. This increase in E-cadherin was partially responsible for the observed alterations in cell morphology and mislocalization of tight junction proteins. We therefore propose the existence of a novel mechanism of cross-talk between specific components of tight and adherens junctions that can be utilized to regulate adhesion between hepatic cells.