Interaction of Integrin αvβ3 with Nectin
IMPLICATION IN CROSS-TALK BETWEEN CELL-MATRIX AND CELL-CELL JUNCTIONS*
- Yasuhisa Sakamoto,
- Hisakazu Ogita,
- Takeshi Hirota,
- Tomomi Kawakatsu,
- Taihei Fukuyama,
- Masato Yasumi,
- Noriyuki Kanzaki,
- Misa Ozaki and
- Yoshimi Takai1
- Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan
- 1 To whom correspondence should be addressed. Tel.: 81-6-6879-3410; Fax: 81-6-6879-3419; E-mail: ytakai{at}molbio.med.osaka-u.ac.jp.
Abstract
Cell-matrix and cell-cell junctions cross-talk together, and these two junctions cooperatively regulate cell movement, proliferation, adhesion, and polarization. However, the mechanism of this cross-talk remains unknown. An immunoglobulin-like cell-cell adhesion molecule nectin first trans-interacts with each other to form cell-cell adhesion and induces activation of Rap1, Cdc42, and Rac small G proteins through c-Src. Trans-interacting nectin then recruits another cell-cell adhesion molecule cadherin to the nectin-based cell-cell adhesion sites and forms adherens junctions (AJs). Here, we show that integrin αvβ3 functionally and physically associates with nectin. Integrin αvβ3 colocalized with nectin at the nectin-based cell-cell adhesion sites. The association of integrin αvβ3 with nectin was direct and was mediated through their extracellular regions. This interaction was necessary for the nectin-induced signaling. Focal adhesion kinase, which relays the integrin-initiated outside-in signals to the intracellular signaling molecules, was also involved in the nectin-induced signaling. During the formation of AJs, the high affinity form of integrin αvβ3 co-localized with nectin at the primordial cell-cell contact sites, and then after the establishment of AJs, this high affinity form of integrin αvβ3 was converted to the low affinity form, which continued to co-localize with nectin. Thus, integrin αvβ3 and nectin play pivotal roles in the cross-talk between cell-matrix and cell-cell junctions and the formation of cadherin-based AJs.
Footnotes
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↵2 The abbreviations used are: AJ, adherens junction; TJ, tight junction; ECM, extracellular matrix; Necl, nectin-like molecule; Nef, the extracellular fragment of nectin fused to the Fc portion of IgG; DMEM, Dulbecco's modified Eagle's medium; mAb, monoclonal antibody; pAb, polyclonal antibody; FRNK, FAK-related non-kinase; FAK, focal adhesion kinase; HA, hemagglutinin; GFP, green fluorescent protein; FITC, fluorescein isothiocyanate; HEK cell, human embryonic kidney cell; MDCK cell, Madin-Darby canine kidney cell; siRNA, small interfering RNA; GST-PAK-CRIB, glutathione S-transferase-PAK-Cdc42/Rac interactive binding region.
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↵* This work was supported by grants-in-aid for Scientific Research and for Cancer Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (2005 and 2006). The costs of publication of this article were defrayed in part by the payment of page charges. This 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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- Received January 11, 2006.
- Revision received May 2, 2006.
- The American Society for Biochemistry and Molecular Biology, Inc.
