Shin Kunyoo, Wang Qian, Margolis Ben
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109-2200, USA.
EMBO Rep. 2007 Feb;8(2):158-64. doi: 10.1038/sj.embor.7400890. Epub 2007 Jan 19.
Directional migration is important in wound healing by epithelial cells. Recent studies have shown that polarity proteins such as mammalian Partitioning-defective 6 (Par6), atypical protein kinase C (aPKC) and mammalian Discs large 1 (Dlg1) are crucial not only for epithelial apico-basal polarity, but also for directional movement. Here, we show that the protein associated with Lin seven 1 (PALS1)-associated tight junction protein (PATJ), another evolutionarily conserved polarity protein, is also required for directional migration by using a wound-induced migration assay. In addition, we found that aPKC and Par3 localize to the leading edge during migration of epithelia and that PATJ regulates their localization. Furthermore, our results show that microtubule-organizing centre orientation is disrupted in PATJ RNA interference (RNAi) MDCKII (Madin-Darby canine kidney II) cells during migration. Together, our data indicate that PATJ controls directional migration by regulating the localization of aPKC and Par3 to the leading edge. The migration defect in PATJ RNAi cells seems to be due to the disorganization of the microtubule network induced by mislocalization of polarity proteins.
定向迁移在上皮细胞伤口愈合过程中很重要。最近的研究表明，诸如哺乳动物的失裂缺陷蛋白6（Par6）、非典型蛋白激酶C（aPKC）和哺乳动物的大圆盘蛋白1（Dlg1）等极性蛋白不仅对于上皮细胞的顶-基极性至关重要，而且对于定向运动也至关重要。在此，我们通过伤口诱导迁移试验表明，与林七蛋白1（PALS1）相关的紧密连接蛋白（PATJ），另一种进化上保守的极性蛋白，对于定向迁移也是必需的。此外，我们发现上皮细胞迁移过程中aPKC和Par3定位于前沿，并且PATJ调节它们的定位。此外，我们的结果表明，在迁移过程中，PATJ RNA干扰（RNAi）的MDCKII（麦氏犬肾II）细胞中微管组织中心的方向被破坏。总之，我们的数据表明，PATJ通过调节aPKC和Par3定位于前沿来控制定向迁移。PATJ RNAi细胞中的迁移缺陷似乎是由于极性蛋白定位错误诱导的微管网络紊乱所致。
