Direct Interaction of the Rho GDP Dissociation Inhibitor with Ezrin/Radixin/Moesin Initiates the Activation of the Rho Small G Protein*
- Kazuo Takahashi‡§,
- Takuya Sasaki‡,
- Akiko Mammoto‡,
- Kenji Takaishi‡,
- Takaaki Kameyama‡¶,
- Sachiko Tsukita‖,
- Shoichiro Tsukita** and
- Yoshimi Takai‡‡
- From the ‡Department of Molecular Biology and Biochemistry, Osaka University Medical School, Suita 565 and the‖College of Medical Technology and the **Department of Cell Biology, Faculty of Medicine, Kyoto University, Kyoto 606, Japan
Abstract
The Rho GDP dissociation inhibitor (GDI) forms a complex with the GDP-bound form of the Rho family small G proteins and inhibits their activation. The GDP-bound form complexed with Rho GDI is not activated by the GDP/GTP exchange factor for the Rho family members, suggesting the presence of another factor necessary for this activation. We have reported that the Rho subfamily members regulate the ezrin/radixin/moesin (ERM)-CD44 system, implicated in reorganization of actin filaments. Here we report that Rho GDI directly interacts with ERM, initiating the activation of the Rho subfamily members by reducing the Rho GDI activity. These results suggest that ERM as well as Rho GDI and the Rho GDP/GTP exchange factor are involved in the activation of the Rho subfamily members, which then regulate reorganization of actin filaments through the ERM system.
Footnotes
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↵* The work performed at Osaka University Medical School was supported by grants-in-aid for scientific research and for cancer research from the Ministry of Education, Science, Sports, and Culture of Japan, by grants-in-aid for abnormalities in hormone receptor mechanisms and for aging and health from the Ministry of Health and Welfare of Japan, and by grants from the Human Frontier Science Program and the Uehara Memorial Foundation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵§ Present address: Second Dept. of Internal Medicine, Chiba University Medical School, Chiba 260, Japan.
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↵¶ Present address: Dept. of Drug Discovery, Eisai Co. Ltd., Tsukuba 300-26, Japan.
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↵‡ To whom correspondence should be addressed: Dept. of Molecular Biology and Biochemistry, Osaka University Medical School, 2-2 Yamada-oka, Suita 565, Japan. Tel.: 81-6-879-3410; Fax: 81-6-879-3419; E-mail: ytakai{at}molbio.med.osaka-u.ac.jp.
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↵1 The abbreviations used are: GDI, GDP dissociation inhibitor; GEF, GDP/GTP exchange factor; ERM, ezrin/radixin/moesin; GST, glutathione S-transferase; GDP-RhoA, the GDP-bound form of RhoA; CHAPS, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate; HA, hemagglutinin; PBS, phosphate-buffered saline; GTPγS, guanosine 5′-O-(3-thiotriphosphate).
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- Received June 16, 1997.
