E-cadherin is a key cell–cell adhesion molecule at adherens junctions (AJs) and undergoes endocytosis when AJs are disrupted by the action of extracellular signals. To elucidate the mechanism of this endocytosis, we developed here a new cell-free assay system for this reaction using the AJ-enriched fraction from rat liver. We found here that non-trans-interacting, but not trans-interacting, E-cadherin underwent endocytosis in a clathrin-dependent manner. The endocytosis of trans-interacting E-cadherin was inhibited by Rac and Cdc42 small G proteins, which were activated by trans-interacting E-cadherin or trans-interacting nectins, which are known to induce the formation of AJs in cooperation with E-cadherin. This inhibition was mediated by reorganization of the actin cytoskeleton by Rac and Cdc42 through IQGAP1, an actin filament-binding protein and a downstream target of Rac and Cdc42. These results indicate the important role of the Rac/Cdc42-IQGAP1 system in the dynamic organization and maintenance of the E-cadherin–based AJs.
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19 July 2004
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July 19 2004
Endocytosis of E-cadherin regulated by Rac and Cdc42 small G proteins through IQGAP1 and actin filaments
Genkichi Izumi,
Genkichi Izumi
1Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan
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Toshiaki Sakisaka,
Toshiaki Sakisaka
1Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan
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Takeshi Baba,
Takeshi Baba
1Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan
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Shintaro Tanaka,
Shintaro Tanaka
1Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan
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Koji Morimoto,
Koji Morimoto
2KAN Research Institute Inc., Kyoto 600-8815, Japan
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Yoshimi Takai
Yoshimi Takai
1Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan
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Genkichi Izumi
1Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan
Toshiaki Sakisaka
1Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan
Takeshi Baba
1Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan
Shintaro Tanaka
1Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan
Koji Morimoto
2KAN Research Institute Inc., Kyoto 600-8815, Japan
Yoshimi Takai
1Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan
Address correspondence to Yoshimi Takai, Dept. of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan. Tel.: 81-6-6879-3410. Fax: 81-6-6879-3419. email: [email protected]
Abbreviations used in this paper: AJ, adherens junction; CAMs, cell–cell adhesion molecules; CCV, clathrin-coated vesicle; HSP, high-speed pellet; Lat-A, latrunculin A; MSP, medium-speed pellet; MSS, medium-speed supernatant.
Received:
June 04 2004
Accepted:
June 07 2004
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2004
J Cell Biol (2004) 166 (2): 237–248.
Article history
Received:
June 04 2004
Accepted:
June 07 2004
Citation
Genkichi Izumi, Toshiaki Sakisaka, Takeshi Baba, Shintaro Tanaka, Koji Morimoto, Yoshimi Takai; Endocytosis of E-cadherin regulated by Rac and Cdc42 small G proteins through IQGAP1 and actin filaments . J Cell Biol 19 July 2004; 166 (2): 237–248. doi: https://doi.org/10.1083/jcb.200401078
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