Involvement of IQGAP1, an effector of Rac1 and Cdc42 GTPases, in cell-celldissociation during cell scattering

We have previously proposed that IQGAP1, an effector of Rad and Cdc42, nega tively regulates cadherin-mediated cell-cell adhesion by interacting with b eta -catenin and by causing the dissociation of alpha -catenin from cadheri n-beta -catenin-alpha -catenin complexes and that activated Rad and Cdc42 p ositively regulate cadherin-mediated cell-cell adhesion by inhibiting the i nteraction of IQGAP1 with beta -catenin. However, it remains to be clarifie d in which physiological processes the Rac1-Cdc42-IQGAP1 system is involved . We here examined whether the Rac1-IQGAP1 system is involved in the cell-c ell dissociation of Madin-Darby canine kidney II cells during 12-O-tetradec anoylphorbol-13-acetate (TPA)- or hepatocyte growth factor (HGF)-induced ce ll scattering. By using enhanced green fluorescent protein (EGFP)-tagged al pha -catenin, we found that EGFP-alpha -catenin decreased prior to cell-cel l dissociation during cell scattering. We also found that the Rac1-GTP leve l decreased after stimulation with TPA and that the Rac1-IQGAP1 complexes d ecreased, while the IQGAP1-beta -catenin complexes increased during action of TPA. Constitutively active Rad and IQGAP1 carboxyl terminus, a putative dominant-negative mutant of IQGAP1, inhibited the disappearance of alpha -c atenin from sites of cell-cell contact induced by TPA. Taken together, thes e results indicate that alpha -catenin is delocalized from cell-cell contac t sites prior to cell-cell dissociation induced by TPA or HGF and suggest t hat the Rac1-IQGAP1 system is involved in cell-cell dissociation through al pha -catenin relocalization.