Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
J Cell Sci. 2011 May 1;124(Pt 9):1589-600. doi: 10.1242/jcs.073916. Epub 2011 Apr 12.
The tumor suppressor Adenomatous polyposis coli (APC) has roles in both Wnt signaling and in actin and microtubule organization. Within the cell, APC proteins have been reported to localize in the cytoplasm, at the cell cortex and in the nucleus. How these localizations relate to the functions of the protein is an aspect of APC biology that is poorly understood. Using Drosophila S2 cells, we have dissected the structural and functional requirements for the cortical localization of Drosophila APC2. Here, we show that both the Armadillo repeats and a novel C-terminal domain are necessary for the cortical localization of APC2 in S2 cells and in the embryo, and that neither domain alone is sufficient for this localization. Furthermore, we show that the Armadillo repeats mediate self-association of APC2 molecules. To test the function of the cortical localization of APC2, we asked whether an APC2 protein deleted for the C-terminal localization domain could rescue APC mutant defects in Wnt signaling and actin organization in the Drosophila embryo. We show that although cortical localization is required for the APC2 function in organizing actin, cortical localization is dispensable for its role in regulating Wnt signaling.
肿瘤抑制因子腺瘤性结肠息肉病（APC）在 Wnt 信号传导以及肌动蛋白和微管组织中都有作用。在细胞内，已经报道 APC 蛋白定位于细胞质、细胞膜和细胞核中。这些定位与蛋白质功能之间的关系是 APC 生物学中理解不足的一个方面。使用果蝇 S2 细胞，我们已经解析了果蝇 APC2 皮质定位的结构和功能要求。在这里，我们表明 Armadillo 重复序列和一个新的 C 末端结构域对于 APC2 在 S2 细胞和胚胎中的皮质定位都是必需的，而且这两个结构域单独都不足以实现这种定位。此外，我们表明 Armadillo 重复序列介导 APC2 分子的自我缔合。为了测试 APC2 皮质定位的功能，我们询问了是否可以通过删除 APC2 蛋白的 C 末端定位结构域来拯救 APC 突变在果蝇胚胎中 Wnt 信号传导和肌动蛋白组织中的缺陷。我们表明，尽管 APC2 的皮质定位对于肌动蛋白的组织是必需的，但对于调节 Wnt 信号的作用来说，皮质定位是可有可无的。
