Involvement of IQGAP1, an Effector of Rac1 and Cdc42 GTPases, in Cell-Cell Dissociation during Cell Scattering

doi:10.1128/MCB.21.6.2165-2183.2001

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Molecular and Cellular Biology, March 2001, p. 2165-2183, Vol. 21, No. 6
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.6.2165-2183.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Involvement of IQGAP1, an Effector of Rac1 and Cdc42 GTPases, in Cell-Cell Dissociation during Cell Scattering

Masaki Fukata,¹^,² Masato Nakagawa,¹ Naohiro Itoh,¹ Aie Kawajiri,¹ Masaki Yamaga,¹ Shinya Kuroda,¹^, and Kozo Kaibuchi¹^,²^,^*

Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma 630-0101,¹ and Department of Cell Pharmacology, Nagoya University, Graduate School of Medicine, Showa, Nagoya 466-8550,² Japan

Received 3 November 2000/Accepted 28 December 2000

We have previously proposed that IQGAP1, an effector of Rac1 and Cdc42, negatively regulates cadherin-mediated cell-cell adhesionby interacting with $beta$ -catenin and by causing the dissociationof $alpha$ -catenin from cadherin- $beta$ -catenin- $alpha$ -catenin complexes and thatactivated Rac1 and Cdc42 positively regulate cadherin-mediatedcell-cell adhesion by inhibiting the interaction of IQGAP1 with $beta$ -catenin. However, it remains to be clarified in which physiologicalprocesses the Rac1-Cdc42-IQGAP1 system is involved. We here examinedwhether the Rac1-IQGAP1 system is involved in the cell-cell dissociationof Madin-Darby canine kidney II cells during 12-O-tetradecanoylphorbol-13-acetate(TPA)- or hepatocyte growth factor (HGF)-induced cell scattering.By using enhanced green fluorescent protein (EGFP)-tagged $alpha$ -catenin,we found that EGFP- $alpha$ -catenin decreased prior to cell-cell dissociationduring cell scattering. We also found that the Rac1-GTP leveldecreased after stimulation with TPA and that the Rac1-IQGAP1complexes decreased, while the IQGAP1- $beta$ -catenin complexes increasedduring action of TPA. Constitutively active Rac1 and IQGAP1 carboxylterminus, a putative dominant-negative mutant of IQGAP1, inhibitedthe disappearance of $alpha$ -catenin from sites of cell-cell contactinduced by TPA. Taken together, these results indicate that $alpha$ -cateninis delocalized from cell-cell contact sites prior to cell-celldissociation induced by TPA or HGF and suggest that the Rac1-IQGAP1system is involved in cell-cell dissociation through $alpha$ -cateninrelocalization.

^* Corresponding author. Mailing address: Division of Signal Transduction, Nara Institute of Science and Technology, 8916-5 Takayama,Ikoma 630-0101, Japan. Phone: 81-743-72-5440. Fax: 81-743-72-5449.E-mail: kaibuchi{at}bs.aist-nara.ac.jp.

Present address: Center for Neurobiology and Behavior, Columbia University, New York, NY10032.

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