Department of Biology, Stanford University, Stanford, CA 94304, USA.
Development. 2012 Feb;139(3):537-46. doi: 10.1242/dev.073932. Epub 2011 Dec 21.
αE-catenin is an actin-binding protein associated with the E-cadherin-based adherens junction that regulates cell-cell adhesion. Recent studies identified additional E-cadherin-independent roles of αE-catenin in regulating plasma membrane dynamics and cell migration. However, little is known about the roles of αE-catenin in these different cellular processes in vivo during early vertebrate development. Here, we examined the functions of αE-catenin in cell-cell adhesion, cell migration and plasma membrane dynamics during morphogenetic processes that drive epiboly in early Danio rerio (zebrafish) development. We show that depletion of αE-catenin caused a defect in radial intercalation that was associated with decreased cell-cell adhesion, in a similar manner to E-cadherin depletion. Depletion of αE-catenin also caused deep cells to have protracted plasma membrane blebbing, and a defect in plasma membrane recruitment of ERM proteins that are involved in controlling membrane-to-cortex attachment and membrane blebbing. Significantly, depletion of both E-cadherin and αE-catenin suppressed plasma membrane blebbing. We suggest that during radial intercalation the activities of E-cadherin and αE-catenin in the maintenance of membrane-to-cortex attachment are balanced, resulting in stabilization of cell-cell adhesion and suppression of membrane blebbing, thereby enabling proper radial intercalation.
αE-连环蛋白是一种与 E-钙黏蛋白基黏附连接相关的肌动蛋白结合蛋白，调节细胞-细胞黏附。最近的研究确定了 αE-连环蛋白在调节质膜动力学和细胞迁移方面的另外一些不依赖 E-钙黏蛋白的作用。然而，在早期脊椎动物发育过程中，在体内，关于 αE-连环蛋白在这些不同细胞过程中的作用，人们知之甚少。在这里，我们研究了 αE-连环蛋白在形态发生过程中的细胞-细胞黏附、细胞迁移和质膜动力学中的功能，这些过程驱动早期 Danio rerio（斑马鱼）发育中的胚环运动。我们发现，αE-连环蛋白的耗竭导致了径向内插的缺陷，这与细胞-细胞黏附的减少有关，这与 E-钙黏蛋白的耗竭相似。αE-连环蛋白的耗竭还导致深层细胞的质膜泡状突起延长，并且涉及控制膜与皮质附着和质膜泡状突起的 ERM 蛋白的质膜募集出现缺陷。重要的是，E-钙黏蛋白和 αE-连环蛋白的耗竭都抑制了质膜泡状突起。我们认为，在径向内插过程中，E-钙黏蛋白和 αE-连环蛋白在维持膜与皮质附着中的活性是平衡的，从而稳定细胞-细胞黏附并抑制质膜泡状突起，从而使适当的径向内插成为可能。
