Cortactin is necessary for E-cadherin-mediated contact formation and actin reorganization
Cortactin is necessary for E-cadherin-mediated contact formation and actin reorganization
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DOI：
10.1083/jcb.200309034
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发表时间：
2004-03-15
影响因子：
7.8
通讯作者：
Yap, AS
中科院分区：
文献类型：
--
作者：
Helwani, FM;Kovacs, EM;Yap, AS
经典的钙粘蛋白粘附分子是发育过程和胚胎后生命中细胞间识别的关键决定因素。基于钙粘蛋白的高效识别的决定性步骤是将新生粘附转化为稳定的接触区。越来越清楚的是，这种接触区的延伸需要钙粘蛋白粘附和肌动蛋白细胞骨架的力产生能力之间的积极配合。 Cortactin 最近已成为多种形式的细胞运动中肌动蛋白动力学的重要调节剂。我们现在报告说，皮质蛋白被募集到细胞与细胞的粘附接触中，以响应同源钙粘蛋白连接。值得注意的是，cortactin 与 Arp2/3 一起优先积聚在粘附接触延伸的细胞边缘。皮质蛋白的募集伴随着皮质蛋白和钙粘蛋白粘附复合物之间的连接依赖性生化相互作用。抑制细胞中的皮质蛋白活性可阻断钙粘蛋白粘附接触处的 Arp2/3 依赖性肌动蛋白组装，显着减少钙粘蛋白粘附接触区的延伸，并扰乱细胞形态和极化上皮中钙粘蛋白的连接积累。总之，我们的研究结果确定了皮质蛋白在支持有效接触形成的钙粘蛋白-肌动蛋白合作中的必要作用。
Classical cadherin adhesion molecules are key determinants of cell-cell recognition during development and in post-embryonic life. A decisive step in productive cadherin-based recognition is the conversion of nascent adhesions into stable zones of contact. It is increasingly clear that such contact zone extension entails active cooperation between cadherin adhesion and the force-generating capacity of the actin cytoskeleton. Cortactin has recently emerged as an important regulator of actin dynamics in several forms of cell motility. We now report that cortactin is recruited to cell-cell adhesive contacts in response to homophilic cadherin ligation. Notably, cortactin accumulates preferentially, with Arp2/3, at cell margins where adhesive contacts are being extended. Recruitment of cortactin is accompanied by a ligation-dependent biochemical interaction between cortactin and the cadherin adhesive complex. Inhibition of cortactin activity in cells blocked Arp2/3-dependent actin assembly at cadherin adhesive contacts, significantly reduced cadherin adhesive contact zone extension, and perturbed both cell morphology and junctional accumulation of cadherins in polarized epithelia. Together, our findings identify a necessary role for cortactin in the cadherin-actin cooperation that supports productive contact formation.