Cortactin Scaffolds Arp2/3 and WAVE2 at the Epithelial Zonula Adherens
Cortactin Scaffolds Arp2/3 and WAVE2 at the Epithelial Zonula Adherens
复制标题
DOI：
10.1074/jbc.m113.544478
复制
发表时间：
2014-03-14
影响因子：
4.8
通讯作者：
Yap, Alpha S.
中科院分区：
文献类型：
--
作者：
Han, Siew Ping;Gambin, Yann;Yap, Alpha S.
背景：上皮细胞间的有效相互作用需要肌动蛋白丝在E-钙粘蛋白粘附处的组装。结果如下：Cordyn通过与E-cadherin和N-WASP的相互作用定位于粘附小带;在那里它通过单独的机制招募Arp 2/3和WAVE 2以支持肌动蛋白成核。结论：Cordyn具有良好的支架作用。重要性：钙粘蛋白连接是细胞粘附、信号传导和细胞骨架相互作用的结果，钙粘蛋白与肌动蛋白之间的动态整合是由钙粘蛋白与细胞骨架相互作用的结果。在粘附小带（ZA），WAVE 2-Arp 2/3肌动蛋白成核装置是必要的连接张力和完整性。但这是如何与钙粘蛋白粘附协调尚不清楚。我们现在确定corneumen作为一个关键的支架肌动蛋白调节在ZA，其本地化的ZA，通过影响E-cadherin和N-WASP。使用无细胞蛋白表达和荧光单分子符合分析，我们证明，corneum直接结合到钙粘蛋白的胞质尾。然而，其与钙粘蛋白在顶端ZA的浓度也需要N-WASP。已知Corpine直接结合Arp 2/3（Weed，S.一、Karginov，A.五、Schafer，D.一、Weaver，A. M.，Kinley，A. W.，库珀，J.A.，和Parsons，J.T.（2000）J. Cell Biol.151，29-40）。我们进一步表明，corneum可以直接绑定WAVE 2，以及Arp 2/3，这两个相互作用是必要的肌动蛋白组装在ZA。我们建议，corneum作为一个平台，整合监管机构的连接肌动蛋白组装在ZA。
Background: Productive epithelial interactions require actin filament assembly at E-cadherin adhesions. Results: Cortactin localizes to the zonula adherens through interactions with E-cadherin and N-WASP; there it recruits Arp2/3 and WAVE2 by separate mechanisms to support actin nucleation. Conclusion: Cortactin acts as a coincident scaffold. Significance: Cortactin can regulate the dynamic integration of cadherin adhesion with the actin cytoskeleton.Cadherin junctions arise from the integrated action of cell adhesion, signaling, and the cytoskeleton. At the zonula adherens (ZA), a WAVE2-Arp2/3 actin nucleation apparatus is necessary for junctional tension and integrity. But how this is coordinated with cadherin adhesion is not known. We now identify cortactin as a key scaffold for actin regulation at the ZA, which localizes to the ZA through influences from both E-cadherin and N-WASP. Using cell-free protein expression and fluorescent single molecule coincidence assays, we demonstrate that cortactin binds directly to the cadherin cytoplasmic tail. However, its concentration with cadherin at the apical ZA also requires N-WASP. Cortactin is known to bind Arp2/3 directly (Weed, S. A., Karginov, A. V., Schafer, D. A., Weaver, A. M., Kinley, A. W., Cooper, J. A., and Parsons, J. T. (2000) J. Cell Biol. 151, 29-40). We further show that cortactin can directly bind WAVE2, as well as Arp2/3, and both these interactions are necessary for actin assembly at the ZA. We propose that cortactin serves as a platform that integrates regulators of junctional actin assembly at the ZA.