Wodarz Andreas, Stewart Daniel B, Nelson W James, Nusse Roel
Howard Hughes Medical Institute and Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
J Cell Sci. 2006 Jun 15;119(Pt 12):2425-34. doi: 10.1242/jcs.02973. Epub 2006 May 23.
Armadillo, the Drosophila homolog of beta-catenin, plays a crucial role in both the Wingless signal transduction pathway and cadherin-mediated cell-cell adhesion, raising the possibility that Wg signaling affects cell adhesion. Here, we use a tissue culture system that allows conditional activation of the Wingless signaling pathway and modulation of E-cadherin expression levels. We show that activation of the Wingless signaling pathway leads to the accumulation of hypophosphorylated Armadillo in the cytoplasm and in cellular processes, and to a concomitant reduction of membrane-associated Armadillo. Activation of the Wingless pathway causes a loss of E-cadherin from the cell surface, reduced cell adhesion and increased spreading of the cells on the substratum. After the initial loss of E-cadherin from the cell surface, E-cadherin gene expression is increased by Wingless. We suggest that Wingless signaling causes changes in Armadillo levels and subcellular localization that result in a transient reduction of cadherin-mediated cell adhesion, thus facilitating cell shape changes, division and movement of cells in epithelial tissues.
犰狳（Armadillo）是果蝇中β-连环蛋白的同源物，在无翅（Wingless）信号转导途径和钙黏蛋白介导的细胞间黏附中都起着关键作用，这增加了无翅信号影响细胞黏附的可能性。在此，我们使用一种组织培养系统，该系统允许无翅信号通路的条件性激活以及E-钙黏蛋白表达水平的调节。我们发现，无翅信号通路的激活导致低磷酸化的犰狳在细胞质和细胞突起中积累，并伴随膜相关犰狳的减少。无翅通路的激活导致E-钙黏蛋白从细胞表面丢失，细胞黏附减少，细胞在基质上的铺展增加。在E-钙黏蛋白最初从细胞表面丢失后，无翅信号会增加E-钙黏蛋白基因的表达。我们认为，无翅信号会导致犰狳水平和亚细胞定位的变化，从而导致钙黏蛋白介导的细胞黏附暂时减少，进而促进上皮组织中细胞的形态变化、分裂和移动。
