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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,dagger 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 adhesion by interacting with beta -catenin and by causing the dissociation of alpha -catenin from cadherin-beta -catenin-alpha -catenin complexes and that activated Rac1 and Cdc42 positively regulate cadherin-mediated cell-cell adhesion by inhibiting the interaction of IQGAP1 with beta -catenin. However, it remains to be clarified in which physiological processes the Rac1-Cdc42-IQGAP1 system is involved. We here examined whether the Rac1-IQGAP1 system is involved in the cell-cell dissociation of 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 dissociation during cell scattering. We also found that the Rac1-GTP level decreased after stimulation with TPA and that the Rac1-IQGAP1 complexes decreased, while the IQGAP1-beta -catenin complexes increased during action of TPA. Constitutively active Rac1 and IQGAP1 carboxyl terminus, a putative dominant-negative mutant of IQGAP1, inhibited the disappearance of alpha -catenin from sites of cell-cell contact induced by TPA. Taken together, these results indicate that alpha -catenin is delocalized from cell-cell contact sites prior to cell-cell dissociation induced by TPA or HGF and suggest that the Rac1-IQGAP1 system is involved in cell-cell dissociation through alpha -catenin relocalization.


* 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.

dagger Present address: Center for Neurobiology and Behavior, Columbia University, New York, NY 10032.


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.



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