Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, England, UK.
J Cell Biol. 2013 Jun 10;201(6):887-901. doi: 10.1083/jcb.201211159.
Distributing junctional components around the cell periphery is key for epithelial tissue morphogenesis and homeostasis. We discovered that positioning of dynamic microtubules controls the asymmetric accumulation of E-cadherin. Microtubules are oriented preferentially along the dorso-ventral axis in Drosophila melanogaster embryonic epidermal cells, and thus more frequently contact E-cadherin at dorso-ventral cell-cell borders. This inhibits RhoGEF2, reducing membrane recruitment of Rho-kinase, and increasing a specific E-cadherin pool that is mobile when assayed by fluorescence recovery after photobleaching. This mobile E-cadherin is complexed with Bazooka/Par-3, which in turn is required for normal levels of mobile E-cadherin. Mobile E-cadherin-Bazooka prevents formation of multicellular rosette structures and cell motility across the segment border in Drosophila embryos. Altogether, the combined action of dynamic microtubules and Rho signaling determines the level and asymmetric distribution of a mobile E-cadherin-Bazooka complex, which regulates cell behavior during the generation of a patterned epithelium.
细胞边缘分布的连接成分对于上皮组织形态发生和稳态至关重要。我们发现,动态微管的定位控制着 E-钙黏蛋白的不对称积累。在黑腹果蝇胚胎表皮细胞中,微管优先沿着背腹轴取向,因此更频繁地与背腹细胞-细胞边界处的 E-钙黏蛋白接触。这抑制了 RhoGEF2,减少了 Rho 激酶的膜募集,并增加了在荧光恢复后光漂白测定中具有流动性的特定 E-钙黏蛋白池。这种可移动的 E-钙黏蛋白与 Bazooka/Par-3 复合,这反过来又需要正常水平的可移动 E-钙黏蛋白。可移动的 E-钙黏蛋白-Bazooka 防止了多细胞玫瑰花结结构的形成和果蝇胚胎中跨节边界的细胞迁移。总之,动态微管和 Rho 信号的联合作用决定了可移动的 E-钙黏蛋白-Bazooka 复合物的水平和不对称分布,这调节了模式化上皮形成过程中的细胞行为。