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首页> 外文期刊>American Journal of Physiology >JAM-A is both essential and inhibitory to development of hepatic polarity in WIF-B cells
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JAM-A is both essential and inhibitory to development of hepatic polarity in WIF-B cells

机译：JAM-A对WIF-B细胞肝极性的发展既必不可少又具有抑制作用

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First published December 20, 2007; doi:10.1152/ajpgi.00159.2007.-Junctional adhesion molecule (JAM) is involved in tight junction (TJ) formation in epithelial cells. Three JAMs (A, B, and C) are expressed in rat hepatocytes, but only rat JAM-A is present in polarized WIF-B cells, a rat-human hepatic line. We used knockdown (KD) and overexpression in WIF-B cells to determine the role of JAM-A in the development of hepatic polarity. Expression of rat JAM-A short hairpin RNA resulted in -50% KD of JAM-A and substantial loss of hepatic polarity, as measured by the absence of apical cysts formed by adjacent cells and sealed by TJ belts. When inhibitory RNA-resistant human JAM-A (huWT) was expressed in KD cells, hepatic polarity was restored. In contrast, expression of JAM-A that either lacked its PDZ-binding motif (huAC-term) or harbored a point mutation (T273A) did not complement, indicating that multiple sites within JAM-A's cytoplasmic tail are required for the development of hepatic polarity. Over-expression of huWT in normal WIF-B cells unexpectedly blocked WIF-B maturation to the hepatic phenotype, as did expression of three huJAM-A constructs with single point mutations in putative phosphorylation sites. In contrast, huAC-term was without effect, and the T273A mutant only partially blocked maturation. Our results show that JAM-A is essential for the development of polarity in cultured hepatic cells via its possible phosphorylation and recruitment of relevant PDZ proteins and that hepatic polarity is achieved within a narrow range of JAM-A expression levels. Importantly, formation/ maintenance of TJs and the apical domain in hepatic cells are linked, unlike simple epithelia.
机译：首次发布于2007年12月20日; doi：10.1152 / ajpgi.00159.2007.-接合黏附分子（JAM）参与上皮细胞的紧密连接（TJ）形成。大鼠肝细胞中表达了三种JAM（A，B和C），但极化的WIF-B细胞（大鼠-人肝细胞系）中仅存在大鼠JAM-A。我们在WIF-B细胞中使用了敲低（KD）和过度表达来确定JAM-A在肝极性发展中的作用。大鼠JAM-A短发夹RNA的表达导致JAM-A的KD为-50％，肝极性显着丧失，这是通过不存在由相邻细胞形成并由TJ带密封的顶囊肿来衡量的。当在KD细胞中表达抑制性的耐RNA的人类JAM-A（huWT）时，肝极性得以恢复。相反，缺少PDZ结合基序（huAC-term）或带有点突变（T273A）的JAM-A的表达不互补，表明JAM-A胞质尾巴中的多个位点是肝细胞发育所必需的极性。正常WIF-B细胞中huWT的过度表达出乎意料地阻止了WIF-B成熟至肝表型，在假定的磷酸化位点中，三个具有单点突变的huJAM-A构建体的表达也是如此。相反，huAC-term没有作用，而T273A突变体仅部分阻止了成熟。我们的结果表明，JAM-A通过其可能的磷酸化和募集相关的PDZ蛋白，对于培养的肝细胞中的极性发育至关重要，并且肝脏的极性在JAM-A表达水平的狭窄范围内得以实现。重要的是，与简单的上皮细胞不同，TJs的形成/维持与肝细胞的顶端结构域是相互联系的。

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