Cooperative roles of Par-3 and afadin in the formation of adherens and tight junctions
Cooperative roles of Par-3 and afadin in the formation of adherens and tight junctions
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DOI：
10.1242/jcs.03470
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发表时间：
2007-07-15
影响因子：
4
通讯作者：
Takai, Yoshimi
中科院分区：
文献类型：
--
作者：
Ooshio', Takako;Fujita, Naoyuki;Takai, Yoshimi
Par-3是一种调节上皮细胞紧密连接（TJs）形成的细胞极性蛋白，其中claudin是主要的细胞-细胞粘附分子（CAM）。tj形成于粘附连接（AJs）的顶端侧，其中E-cadherin和connectin是主要的cam。我们发现连接蛋白首先形成细胞-细胞粘附，然后将钙粘蛋白招募到连接蛋白为基础的细胞-细胞粘附位点形成AJs，随后将claudin招募到AJs的顶端形成TJs。连接素的细胞质尾部与腺嘌呤和Par-3结合。Afadin与nectin协同调节AJs和TJs的形成。在这里，我们通过敲除par3的MDCK细胞研究了par3在这些连接形成中的作用。Par-3对于AJs和TJs的形成是必需的，但对于基于连接素的细胞-细胞粘附不是必需的。Par-3促进了afadin与连接蛋白的结合，而afadin对于Par-3与连接蛋白的结合并不是必需的。然而，afadin与连接素的单独作用不足以形成AJs或TJs， Par-3和afadin共同调节AJs或TJs的形成。我们在这里描述了Par-3在连接复合物形成中的这些新作用。
Par-3 is a cell-polarity protein that regulates the formation of tight junctions (TJs) in epithelial cells, where claudin is a major cell- cell adhesion molecule (CAM). TJs are formed at the apical side of adherens junctions (AJs), where E-cadherin and nectin are major CAMs. We have revealed that nectin first forms cell- cell adhesions, and then recruits cadherin to nectin- based cell- cell adhesion sites to form AJs and subsequently recruits claudin to the apical side of AJs to form TJs. The cytoplasmic tail of nectin binds afadin and Par-3. Afadin regulates the formation of AJs and TJs cooperatively with nectin. Here, we studied the role of Par-3 in the formation of these junctions by using Par-3-knockdown MDCK cells. Par-3 was necessary for the formation of AJs and TJs but was not necessary for nectin-based cell-cell adhesion. Par-3 promoted the association of afadin with nectin, whereas afadin was not necessary for the association of Par-3 with nectin. However, the association of afadin with nectin alone was not sufficient for the formation of AJs or TJs, and Par-3 and afadin cooperatively regulated it. We describe here these novel roles of Par-3 in the formation of junctional complexes.