Self-association of PAR-3-mediated by the conserved N-terminal domain contributes to the development of epithelial tight junctions
Self-association of PAR-3-mediated by the conserved N-terminal domain contributes to the development of epithelial tight junctions
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DOI：
10.1074/jbc.m303593200
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发表时间：
2003-08-15
影响因子：
4.8
通讯作者：
Ohno, S
中科院分区：
文献类型：
--
作者：
Mizuno, K;Suzuki, A;Ohno, S
PAR-3是一种支架样含PDZ蛋白，与PAR-6和非典型蛋白激酶C形成复合物（PAR-3-非典型蛋白激酶C-PAR-6复合物），并有助于在多种生物学环境中建立细胞极性。在哺乳动物上皮细胞中，它定位于紧密连接，上皮细胞-细胞连接的最顶端，并有助于功能性紧密连接的形成。然而，PAR-3定位于紧密连接并促进其形成的机制仍有待澄清。在这里，我们表明，N-末端保守区，CR 1-（1-86），和序列937- 1，024所需的招聘到最顶端侧的上皮Madin-Darby犬肾细胞的细胞接触区。我们还表明，CR 1自我协会在体内和体外形成一个寡聚复合物。此外，CR 1在Madin-Darby犬肾细胞中的过表达扰乱了非典型蛋白激酶C和PAR-6以及PAR-3的分布，并延迟了功能性紧密连接的形成。这些结果支持的概念，CR 1介导的自我协会的PAR-3蛋白复合物在功能性紧密连接的形成过程中发挥作用。
PAR-3 is a scaffold-like PDZ-containing protein that forms a complex with PAR-6 and atypical protein kinase C (PAR-3-atypical protein kinase C-PAR-6 complex) and contributes to the establishment of cell polarity in a wide variety of biological contexts. In mammalian epithelial cells, it localizes to tight junctions, the most apical end of epithelial cell-cell junctions, and contributes to the formation of functional tight junctions. However, the mechanism by which PAR-3 localizes to tight junctions and contributes to their formation remains to be clarified. Here we show that the N-terminal conserved region, CR1-(1-86), and the sequence 937-1,024 are required for its recruitment to the most apical side of the cell-cell contact region in epithelial Madin-Darby canine kidney cells. We also show that CR1 self-associates to form an oligomeric complex in vivo and in vitro. Further, overexpression of CR1 in Madin-Darby canine kidney cells disturbs the distribution of atypical protein kinase C and PAR-6 as well as PAR-3 and delays the formation of functional tight junctions. These results support the notion that the CR1- mediated self-association of the PAR-3-containing protein complex plays a role during the formation of functional tight junctions.