Establishment of cell polarity by afadin during the formation of embryoid bodies
Establishment of cell polarity by afadin during the formation of embryoid bodies
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DOI：
10.1111/j.1365-2443.2007.01150.x
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发表时间：
2008-01-01
期刊：
影响因子：
2.1
通讯作者：
Takai, Yoshimi
中科院分区：
文献类型：
--
作者：
Komura, Hitomi;Ogita, Hisakazu;Takai, Yoshimi
阿法丁直接连接连接蛋白，免疫球蛋白样细胞-细胞粘附分子，肌动蛋白丝（F-肌动蛋白）在粘附连接（AJs）。连接蛋白-阿法丁复合物不仅对AJs的形成很重要，而且对上皮细胞中紧密连接（TJ）的形成也很重要。使用afadin敲除小鼠的研究表明，afadin通过组织细胞间连接的形成对胚胎发育是不可或缺的。然而，对afadin基因敲除小鼠胚胎发育过程中细胞-细胞连接紊乱的分子机制知之甚少。为了解决这个问题，我们利用胚状体（EBs）作为模型系统。在afadin无效的EB中，包括AJs和TJ的细胞-细胞连接的形成受损。Par复合物的适当积累以及Cdc 42和非典型PKC（aPKC）的活化也被afadin的敲除抑制，这对于细胞极性的形成至关重要。此外，afadin的破坏引起层粘连蛋白的异常沉积及其受体整合素α（6）和整合素β（1）的移位。这些结果表明，afadin通过调节早期胚胎发育中的细胞极化来组织细胞-细胞连接的形成。
Afadin directly links nectin, an immunoglobulin-like cell-cell adhesion molecule, to actin filaments (F-actin) at adherens junctions (AJs). The nectin-afadin complex is important for the formation of not only AJs but also tight junctions (TJs) in epithelial cells. Studies using afadin-knockout mice have revealed that afadin is indispensable for embryonic development by organizing the formation of cell-cell junctions. However, the molecular mechanism of cell-cell junction disorganization during embryonic development in afadin-knockout mice is poorly understood. To address this, we took advantage of embryoid bodies (EBs) as a model system. The formation of cell-cell junctions including AJs and TJs was impaired in afadin-null EBs. The proper accumulation of the Par complex and the activation of Cdc42 and atypical PKC (aPKC), which are crucial for the formation of cell polarity, were also inhibited by knockout of afadin. In addition, the disruption of afadin caused the abnormal deposition of laminin and the dislocalization of its receptors integrin alpha(6) and integrin beta(1). These results indicate that afadin organizes the formation of cell-cell junctions by regulating cell polarization in early embryonic development.