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First published online May 12, 2005
doi: 10.1242/10.1242/jcs.02379

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IQGAP1: a key regulator of adhesion and migration

Department of Cell Pharmacology, Nagoya University, Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan

View larger version (16K): [in a new window]   Fig. 1. Schematic representation of IQGAP1 mutants and interacting molecules. The numbers indicate the position of amino acid residues. Abbreviations: CHD, calponin homology domain; WW, domain with two conserved Trp (W) residues; IQGAP repeat, IQGAP-specific repeat motif; IQ motif, calmodulin-binding motif; GRD, RasGAP-related domain; RasGAP C, RasGAP C-terminus; ERK2, extracellular signal-regulated kinase 2; ELC, myosin essential light chain.

View larger version (28K): [in a new window]   Fig. 2. Role of IQGAP1 in the regulation of E-cadherin-mediated cell-cell adhesion. When the amount of activated Rac1 increases, Rac1 interacts with IQGAP1, thereby crosslinking actin filaments. Under these conditions, IQGAP1 does not bind to ß-catenin and cannot dissociate -catenin from the cadherin-catenin complex, leading to strong adhesion. By contrast, when the amounts of inactivated Rac1 increases, IQGAP1 is freed from Rac1 and interacts with ß-catenin to dissociate -catenin from the cadherin-catenin complex. This results in weak adhesion.

View larger version (31K): [in a new window]   Fig. 3. Schematic representation of the movement of microtubules along actin filaments. The coordinated reorganization of the cytoskeleton is essential for cell polarization and migration. Actin filaments are one candidate for guidance tracks for microtubules. Actin-binding proteins such as myosin VI interact with CLIP-190, the Drosophila homolog of CLIP-170, to slide microtubules along actin filaments. In higher eukaryotes, scaffold proteins such as ACF7 link actin filaments and microtubules. These actin-binding proteins and +Tips seem to stabilize mictotubule-actin interactions. They also stabilize cell migration or cell adhesion.

View larger version (25K): [in a new window]   Fig. 4. Role of the IQGAP1-APC complex in cell polarization and migration. Directional cell migration is usually initiated in response to extracellular cues. Extracellular signals, including growth factors and chemokines, activate Rac1 and Cdc42 through their receptors and certain GEFs at leading edges. Activated Rac1 and Cdc42 induce the polymerization of actin filaments through their effectors. Activated Rac1 and Cdc42 also mark spots where IQGAP1 crosslinks actin filaments. There, APC is recruited through IQGAP1 to actin filaments. IQGAP1 captures the plus-ends of microtubules through CLIP-170. APC then directly and/or indirectly stabilizes microtubules, which are necessary for stable actin meshwork at leading edges.