Actin-dependent membrane association of the APC tumour suppressor in polarized mammalian epithelial cells
Actin-dependent membrane association of the APC tumour suppressor in polarized mammalian epithelial cells
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DOI：
10.1093/emboj/20.21.5929
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发表时间：
2001-11-01
期刊：
影响因子：
11.4
通讯作者：
Bienz, M
中科院分区：
文献类型：
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作者：
Rosin-Arbesfeld, R;Ihrke, G;Bienz, M
大肠腺瘤性息肉病（APC）在大多数结直肠癌中发生突变。APC下调细胞核β-连环蛋白，这被认为是其肿瘤抑制功能的关键。然而，APC可能在细胞外围具有额外的和单独的功能。在这里，我们研究极化MDCK和WIF-B肝癌细胞，发现APC与它们的侧质膜相关。这取决于肌动蛋白的细胞骨架，但不是微管，药物洗脱实验表明，APC是通过动态肌动蛋白依赖性过程连续传递到质膜。在极化的MDCK细胞中，APC也聚集在其最基底区域的微管尖端。微管解聚导致APC从这些尖端重新定位到质膜，表明在这些细胞中彼此平衡的两个不同的外周APC池。APC的截短，如在APC突变癌细胞中发现的截短，既不能与质膜结合，也不能与微管尖端结合。APC到达细胞外周的能力可能因此有助于其在肠上皮中的肿瘤抑制功能。
Adenomatous polyposis coli (APC) is mutated in most colorectal cancers. APC downregulates nuclear beta -catenin, which is thought to be critical for its tumour suppressor function. However, APC may have additional and separate functions at the cell periphery. Here, we examine polarized MDCK and WIF-B hepatoma cells and find that APC is associated with their lateral plasma membranes. This depends on the actin cytoskeleton but not on microtubules, and drug wash-out experiments suggest that APC is delivered continuously to the plasma membrane by a dynamic actin-dependent process. In polarized MDCK cells, APC also clusters at microtubule tips in their basal-most regions. Microtubule depolymerization causes APC to relocalize from these tips to the plasma membrane, indicating two distinct peripheral APC pools that are in equilibrium with each other in these cells. Truncations of APC such as those found in APC mutant cancer cells can neither associate with the plasma membrane nor with microtubule tips. The ability of APC to reach the cell periphery may thus contribute to its tumour suppressor function in the intestinal epithelium.