在细胞极化和迁移过程中，与IQGAP1的相互作用将腺瘤性息肉病蛋白（APC）与Rac1、Cdc42和肌动蛋白丝联系起来。
Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration.
作者信息
Watanabe Takashi, Wang Shujie, Noritake Jun, Sato Kazumasa, Fukata Masaki, Takefuji Mikito, Nakagawa Masato, Izumi Nanae, Akiyama Tetsu, Kaibuchi Kozo
机构信息
Department of Cell Pharmacology, Nagoya University, Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi 466-8550, Japan.
出版信息
Dev Cell. 2004 Dec;7(6):871-83. doi: 10.1016/j.devcel.2004.10.017.
Rho family GTPases, particularly Rac1 and Cdc42, are key regulators of cell polarization and directional migration. Adenomatous polyposis coli (APC) is also thought to play a pivotal role in polarized cell migration. We have found that IQGAP1, an effector of Rac1 and Cdc42, interacts directly with APC. IQGAP1 and APC localize interdependently to the leading edge in migrating Vero cells, and activated Rac1/Cdc42 form a ternary complex with IQGAP1 and APC. Depletion of either IQGAP1 or APC inhibits actin meshwork formation and polarized migration. Depletion of IQGAP1 or APC also disrupts localization of CLIP-170, a microtubule-stabilizing protein that interacts with IQGAP1. Taken together, these results suggest a model in which activation of Rac1 and Cdc42 in response to migration signals leads to recruitment of IQGAP1 and APC which, together with CLIP-170, form a complex that links the actin cytoskeleton and microtubule dynamics during cell polarization and directional migration.
Rho家族GTP酶，尤其是Rac1和Cdc42，是细胞极化和定向迁移的关键调节因子。腺瘤性息肉病大肠杆菌（APC）也被认为在极化细胞迁移中起关键作用。我们发现，作为Rac1和Cdc42的效应器，IQGAP1与APC直接相互作用。在迁移的非洲绿猴肾细胞（Vero细胞）中，IQGAP1和APC相互依赖地定位于前沿，并且活化的Rac1/Cdc42与IQGAP1和APC形成三元复合物。IQGAP1或APC的缺失会抑制肌动蛋白网络的形成和极化迁移。IQGAP1或APC的缺失还会破坏CLIP-170（一种与IQGAP1相互作用的微管稳定蛋白）的定位。综上所述，这些结果提示了一种模型，即响应迁移信号而激活的Rac1和Cdc42会导致IQGAP1和APC的募集，它们与CLIP-170一起形成一个复合物，在细胞极化和定向迁移过程中连接肌动蛋白细胞骨架和微管动力学。
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