Loss of Occludin Affects Tricellular Localization of Tricellulin

Loss of Occludin Affects Tricellular Localization of Tricellulin
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DOI:
10.1091/mbc.e08-05-0530
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发表时间:
2008-11-01
影响因子:
3.3
通讯作者:
Tsukita, Shoichiro
Tsukita, Shoichiro
中科院分区:
生物学3区
文献类型:
--
作者:
Ikenouchi, Junichi;Sasaki, Hiroyuki;Tsukita, Shoichiro

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三细胞紧密连接(tTJ)形成于双细胞紧密连接(bTJ)的会聚处,其中三个上皮细胞在极化上皮中相遇,并且其是维持跨上皮屏障所必需的。Tricellulin是一种具有四个跨膜结构域的蛋白质,最近被鉴定为tTJ的第一个标志物,但是关于Tricellulin如何定位于tTJ的知之甚少。至于与紧密连接(TJ)的三纤维素协会的分子机制,我们发现,三纤维素被纳入封闭蛋白为基础的TJ独立的结合到闭合蛋白-1。出乎意料的是,外源表达的三纤维素增加了TJ链在质膜上的交联。至于定位的三细胞连接处的三纤维素的分子机制,我们发现,敲低occludin引起的错误定位的三纤维素bTJ,这意味着occludin支持三细胞定位的三纤维素排除从bTJ的三纤维素。
The tricellular tight junction (tTJ) forms at the convergence of bicellular tight junctions (bTJs) where three epithelial cells meet in polarized epithelia, and it is required for the maintenance of the transepithelial barrier. Tricellulin is a four transmembrane domain protein recently identified as the first marker of tTJ, but little is known about how tricellulin is localized at tTJs. As for the molecular mechanism of association of tricellulin with tight junctions (TJs), we found that tricellulin was incorporated into claudin-based TJs independently of binding to zona occludens-1. Unexpectedly, exogenous expression of tricellulin increased cross-links of TJ strands in the plasma membrane. As for the molecular mechanisms for localization of tricellulin at tricellular junctions, we found that knockdown of occludin caused mislocalization of tricellulin to bTJs, implying that occludin supports tricellular localization of tricellulin by excluding tricellulin from bTJs.