Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration
Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration
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DOI：
10.1016/j.devcel.2004.10.017
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发表时间：
2004-12-01
影响因子：
11.8
通讯作者：
Kaibuchi, K
中科院分区：
文献类型：
--
作者：
Watanabe, T;Wang, SJ;Kaibuchi, K
Rho家族GTP酶，特别是Rac 1和Cdc 42，是细胞极化和定向迁移的关键调节因子。结肠腺瘤性息肉病（APC）也被认为在极化细胞迁移中起关键作用。我们发现IQGAP 1是Rac 1和Cdc 42的效应子，直接与APC相互作用。IQGAP 1和APC在迁移的Vero细胞中相互依赖地定位于前缘，并且激活的Rac 1/Cdc 42与IQGAP 1和APC形成三元复合物。IQGAP 1或APC的耗尽抑制肌动蛋白网络的形成和极化迁移。IQGAP 1或APC的消耗也破坏了CLIP-170的定位，CLIP-170是一种与IQGAP 1相互作用的微管稳定蛋白。综上所述，这些结果表明了一种模型，其中响应于迁移信号的Rac 1和Cdc 42的激活导致IQGAP 1和APC的募集，IQGAP 1和APC与CLIP-170一起形成在细胞极化和定向迁移期间连接肌动蛋白细胞骨架和微管动力学的复合物。
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.