LSR defines cell corners for tricellular tight junction formation in epithelial cells
LSR defines cell corners for tricellular tight junction formation in epithelial cells
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DOI：
10.1242/jcs.072058
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发表时间：
2011-02-15
影响因子：
4
通讯作者：
Furuse, Mikio
中科院分区：
文献类型：
--
作者：
Masuda, Sayuri;Oda, Yukako;Furuse, Mikio
上皮细胞接触不仅包括双细胞接触，还包括三细胞接触，其中三个细胞的角相遇。在三细胞接触时，紧密连接（TJ）产生称为三细胞TJ（tTJ）的专门结构以密封细胞间隙。三纤维素是唯一已知的tTJ分子组分，并且参与tTJ的形成以及正常的上皮屏障功能。然而，tTJ如何形成和维持的详细分子机制仍然难以捉摸。使用基于定位的表达克隆方法，我们确定了一种新的tTJ相关蛋白，称为脂解刺激脂蛋白受体（LSR）。在上皮细胞中LSR敲低后，tTJ形成受到影响，上皮屏障功能减弱。在这些细胞中，三细胞接触处的三纤维素积累也减少。相比之下，LSR仍然积累在三纤维素敲低后的三细胞接触。缺失突变体的分析表明，LSR的胞质结构域是负责招募三纤维素。在这些观察的基础上，我们建议LSR定义三细胞接触上皮细胞片作为一个里程碑，招募tTJ形成的三纤维素。
Epithelial cell contacts consist of not only bicellular contacts but also tricellular contacts, where the corners of three cells meet. At tricellular contacts, tight junctions (TJs) generate specialized structures termed tricellular TJs (tTJs) to seal the intercellular space. Tricellulin is the only known molecular component of tTJs and is involved in the formation of tTJs, as well as in the normal epithelial barrier function. However, the detailed molecular mechanism of how tTJs are formed and maintained remains elusive. Using a localization-based expression cloning method, we identified a novel tTJ-associated protein known as lipolysis-stimulated lipoprotein receptor (LSR). Upon LSR knockdown in epithelial cells, tTJ formation was affected and the epithelial barrier function was diminished. Tricellulin accumulation at the tricellular contacts was also diminished in these cells. By contrast, LSR still accumulated at the tricellular contacts upon tricellulin knockdown. Analyses of deletion mutants revealed that the cytoplasmic domain of LSR was responsible for the recruitment of tricellulin. On the basis of these observations, we propose that LSR defines tricellular contacts in epithelial cellular sheets by acting as a landmark to recruit tricellulin for tTJ formation.