Townsley F M, Bienz M
Laboratory of Molecular Biology, Hills Road, CB2 2QH, Cambridge, UK.
Curr Biol. 2000 Nov 2;10(21):1339-48. doi: 10.1016/s0960-9822(00)00770-3.
The adenomatous polyposis coli (APC) protein is an important tumour suppressor in the colon. It promotes the destabilisation of free cytoplasmic beta-catenin (the vertebrate homologue of the Drosophila protein Armadillo), a critical effector of the Wnt signalling pathway. The beta-catenin protein is also a component of adherens junctions, linking these to the actin cytoskeleton. In Drosophila epithelial cells, the ubiquitous form of APC, known as E-APC, is associated with adherens junctions. This association appears to be necessary for E-APC to function in destabilising Armadillo.
Using actin-depolymerising drugs, we established that an intact actin cytoskeleton is required for the association of E-APC with adherens junctions in the Drosophila embryo. From an analysis of profilin mutants, whose actin cytoskeleton is disrupted, we found that E-APC also requires actin filaments to associate with adhesive cell membranes in the ovary. Notably, conditions that delocalised E-APC from membranes, including a mutation in E-APC itself, caused partial detachment of Armadillo from adhesive membranes.
Actin filaments are continuously required for E-APC to be associated with junctional membranes. These filaments may serve as tracks for E-APC to reach the adherens junctions. The failure of E-APC to do so appears to affect the integrity of junctional complexes.
腺瘤性结肠息肉病蛋白（APC）是结肠中一种重要的肿瘤抑制因子。它能促进游离细胞质β-连环蛋白（果蝇蛋白犰狳的脊椎动物同源物）的不稳定，β-连环蛋白是Wnt信号通路的关键效应物。β-连环蛋白也是黏着连接的一个组成部分，将黏着连接与肌动蛋白细胞骨架相连。在果蝇上皮细胞中，APC的普遍形式，即E-APC，与黏着连接相关。这种关联似乎是E-APC发挥使犰狳不稳定功能所必需的。
使用肌动蛋白解聚药物，我们证实了完整的肌动蛋白细胞骨架是果蝇胚胎中E-APC与黏着连接相关所必需的。通过对肌动蛋白细胞骨架被破坏的原肌球蛋白突变体的分析，我们发现E-APC在卵巢中与黏附细胞膜结合也需要肌动蛋白丝。值得注意的是，使E-APC从膜上脱离定位的条件，包括E-APC自身的突变，导致犰狳从黏附膜上部分脱离。
E-APC与连接膜结合持续需要肌动蛋白丝。这些丝可能作为E-APC到达黏着连接的轨道。E-APC无法做到这一点似乎会影响连接复合体的完整性。
