Binding of APC and dishevelled mediates Wnt5a-regulated focal adhesion dynamics in migrating cells
Binding of APC and dishevelled mediates Wnt5a-regulated focal adhesion dynamics in migrating cells
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DOI：
10.1038/emboj.2010.26
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发表时间：
2010-04-07
期刊：
影响因子：
11.4
通讯作者：
Kikuchi, Akira
中科院分区：
文献类型：
--
作者：
Matsumoto, Shinji;Fumoto, Katsumi;Kikuchi, Akira
Wnt 5a是一种代表性的配体，其激活Wnt/β-连环蛋白非依赖性途径，导致细胞粘附、迁移和极性的调节，但其分子机制知之甚少。该报告显示Dishevelled（Dvl）与腺瘤性结肠息肉病（APC）基因产物结合，并且这种结合被Wnt 5a增强。Dvl参与微管和APC的正端动力学的稳定。Frizzled 2（Fz 2）与Wnt 5a一起存在于迁移细胞的前缘，并通过Dvl与APC形成复合物。Fz 2还在前沿与整合素相互作用，并且Dvl和APC与粘着斑激酶和桩蛋白相关并激活粘着斑激酶和桩蛋白。APC与Dvl的结合增强了桩蛋白在前缘的定位，并参与了Wnt 5a依赖性粘着斑的转换。此外，这种新的Wnt 5a信号通路对于三维培养中的上皮形态发生是重要的。这些结果表明，Dvl和APC的功能和物理相互作用参与了细胞迁移和上皮形态发生过程中的Wnt 5a/Fz 2依赖性粘着斑动力学。The EMBO Journal（2010）29，1192-1204. doi：10.1038/doj.2010.26; 2010年3月11日在线发布
Wnt5a is a representative ligand that activates the Wnt/beta-catenin-independent pathway, resulting in the regulation of cell adhesion, migration, and polarity, but its molecular mechanism is poorly understood. This report shows that Dishevelled (Dvl) binds to adenomatous polyposis coli (APC) gene product, and this binding is enhanced by Wnt5a. Dvl was involved in the stabilization of the plus end dynamics of microtubules as well as APC. Frizzled2 (Fz2) was present with Wnt5a at the leading edge of migrating cells and formed a complex with APC through Dvl. Fz2 also interacted with integrins at the leading edge, and Dvl and APC associated with and activated focal adhesion kinase and paxillin. The binding of APC to Dvl enhanced the localization of paxillin to the leading edge and was involved in Wnt5a-dependent focal adhesion turnover. Furthermore, this new Wnt5a signalling pathway was important for the epithelial morphogenesis in the three-dimensional culture. These results suggest that the functional and physical interaction of Dvl and APC is involved in Wnt5a/Fz2-dependent focal adhesion dynamics during cell migration and epithelial morphogenesis. The EMBO Journal (2010) 29, 1192-1204. doi:10.1038/emboj.2010.26; Published online 11 March 2010