The Tight Junction Protein, Occludin, Regulates the Directional Migration of Epithelial Cells
The Tight Junction Protein, Occludin, Regulates the Directional Migration of Epithelial Cells
复制标题
紧密连接蛋白 Occludin 调节上皮细胞的定向迁移。
DOI：
10.1016/j.devcel.2009.12.008
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发表时间：
2010-01-19
影响因子：
11.8
通讯作者：
Chen, Zhengjun
中科院分区：
文献类型：
--
作者：
Du, Dan;Xu, Feilai;Chen, Zhengjun
细胞极性蛋白调节上皮细胞中紧密连接的形成和定向迁移。迄今为止，这些极性蛋白在迁移上皮细胞前缘组装的机制仍不清楚。我们报道，occludin 是一种跨膜蛋白，位于迁移细胞的前缘并调节细胞的定向迁移。在迁移过程中，occludin 敲低破坏了 aPKC-Par3 和 PATJ 在前缘的积累，并导致微管网络紊乱和微管组织中心 (MTOC) 的重新定向缺陷。 occludin 在酪氨酸 473 残基处的磷酸化允许 p85 α 通过与其 C 端 SH2 结构域关联而募集到前缘。 occludin 的缺失会减弱 PI3K 的激活，导致肌动蛋白细胞骨架解体并减少细胞突起。我们的数据表明，occludin 是极性蛋白 aPKC-Par3 和 PATJ 前沿定位所必需的，并通过调节 PI3K 的膜局部激活来促进细胞突出。
Cell polarity proteins regulate tight junction formation and directional migration in epithelial cells. To date, the mechanism by which these polarity proteins assemble at the leading edge of migrating epithelial cells remains unclear. We report that occludin, a transmembrane protein, is localized at the leading edge of migrating cells and regulates directional cell migration. During migration, occludin knockdown disrupted accumulation of aPKC-Par3 and PATJ at the leading edge, and led to a disorganized microtubule network and defective reorientation of the microtubule organization center (MTOC). Phosphorylation of occludin at tyrosine 473 residue allowed recruitment of p85 alpha to the leading edge via association with its C-terminal SH2 domain. Loss of occludin attenuated activation of PI3K, leading to disorganization of the actin cytoskeleton and reduced cell protrusions. Our data indicate that occludin is required for the leading-edge localization of polarity proteins aPKC-Par3 and PATJ and promotes cell protrusion by regulating membrane-localized activation of PI3K.