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Molecular and Cellular Biology, March 2001, p. 2165-2183, Vol. 21, No. 6
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
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
and
-catenin and by causing the
dissociation of
-catenin from cadherin-
-catenin-
-catenin
complexes and that activated Rac1 and Cdc42 positively regulate
cadherin-mediated cell-cell adhesion by inhibiting the interaction
of IQGAP1 with
-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
-catenin, we found that
EGFP-
-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-
-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
-catenin from sites
of cell-cell contact induced by TPA. Taken together, these results
indicate that
-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
-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.
Present address: Center for Neurobiology and Behavior, Columbia
University, New York, NY 10032.
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