Behavior of tight-junction, adherens-junction and cell polarity proteins during HNF-4α-induced epithelial polarization
Behavior of tight-junction, adherens-junction and cell polarity proteins during HNF-4α-induced epithelial polarization
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DOI：
10.1016/j.yexcr.2005.06.025
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发表时间：
2005-10-15
影响因子：
3.7
通讯作者：
Sawada, N
中科院分区：
文献类型：
--
作者：
Satohisa, S;Chiba, H;Sawada, N
我们之前报道过，在表达肝细胞核因子（HNF）-4 α [H.千叶、T. Gotoh、T. Kojima、S. Satohisa、K. Kikuchi、M. Osanai、N. Sawada。肝细胞核因子 (HNF)-4a 触发 F9 胚胎癌细胞中功能性紧密连接的形成和极化上皮形态的建立，实验。细胞研究。 286（2003）288-297]。使用这些细胞，我们在本研究中检查了紧密连接、粘附连接和细胞极性蛋白的行为，并阐明了 HNF-4 α 启动连接形成和上皮极化背后的分子机制。我们在此表明，不仅 ZO-1 和 ZO-2，而且 ZO-3、连接粘附分子 (JAM)-B、JAM-C 和细胞极性蛋白 PAR-3、PAR-6 和非典型蛋白激酶 C (aPKC) 在未分化的 F9 细胞的原始粘附连接处积累。相比之下，CRB3、Pals1和PATJ似乎在未成熟细胞中表现出不同的亚细胞定位。HNF-4α的诱导表达导致这些紧密连接和细胞极性蛋白易位至带状紧密连接，在分化细胞中组装occludin、claudin-6和claudin-7。有趣的是，PAR-6、aPKC、CRB3 和 Pals1（而非 PAR-3 或 PATJ）也集中在分化细胞的顶膜上。这些发现表明，HNF-4 α 不仅会引发紧密连接粘附分子的表达，还会调节连接和细胞极性蛋白的亚细胞分布，从而导致连接形成和上皮极化。 (c) 2005 Elsevier Inc. 保留所有权利。
We previously reported that expression of tight-junction molecules occludin, claudin-6 and claudin-7, as well as establishment of epithelial polarity, was triggered in mouse F9 cells expressing hepatocyte nuclear factor (HNF)-4 alpha [H. Chiba, T. Gotoh, T. Kojima, S. Satohisa, K. Kikuchi, M. Osanai, N. Sawada. Hepatocyte nuclear factor (HNF)-4a triggers formation of functional tight junctions and establishment of polarized epithelial morphology in F9 embryonal carcinoma cells, Exp. Cell Res. 286 (2003) 288-297]. Using these cells, we examined in the present study behavior of tight-junction, adherens-junction and cell polarity proteins and elucidated the molecular mechanism behind HNF-4 alpha-initiated junction formation and epithelial polarization. We herein show that not only ZO-1 and ZO-2, but also ZO-3, junctional adhesion molecule (JAM)-B, JAM-C and cell polarity proteins PAR-3, PAR-6 and atypical protein kinase C (aPKC) accumulate at primordial adherens junctions in undifferentiated F9 cells. In contrast, CRB3, Pals1 and PATJ appeared to exhibit distinct subcellular localization in immature cells, Induced expression of HNF-4 alpha led to translocation of these tight-junction and cell polarity proteins to beltlike tight junctions, where occludin, claudin-6 and claudin-7 were assembled, in differentiated cells. Interestingly, PAR-6, aPKC, CRB3 and Pals1, but not PAR-3 or PATJ, were also concentrated on the apical membranes in differentiated cells. These findings indicate that HNF-4 alpha provokes not only expression of tight-junction adhesion molecules, but also modulation of subcellular distribution of junction and cell polarity proteins, resulting in junction formation and epithelial polarization. (c) 2005 Elsevier Inc. All rights reserved.