Disruption of Focal Adhesions by Integrin Cytoplasmic Domain-associated Protein-1α

doi:10.1074/jbc.M211258200

Disruption of Focal Adhesions by Integrin Cytoplasmic Domain-associated Protein-1α*

From the ^‡Laboratoire d'Etude de la Differenciation et de l'Adhérence Cellulaires, Unité Mixte de Recherche UJF/CNRS 5538, Institut Albert Bonniot, Faculte de Médecine de Grenoble, La Tronche F38706 cedex, France, the ^‖Department of Genetics, Biology, and Biochemistry, University of Torino, Torino 10126, Italy, and the ^§Department of Molecular Medicine, Max Planck Institute for Biochemistry, Am Klopferspitz 18A, Martinsried D-82152, Germany

Abstract

Regulation of integrin affinity and clustering plays a key role in the control of cell adhesion and migration. The protein ICAP-1α (integrin cytoplasmic domain-associated protein-1α) binds to the cytoplasmic domain of the β_1Aintegrin and controls cell spreading on fibronectin. Here, we demonstrate that, despite its ability to interact with β_1A integrin, ICAP-1α is not recruited in focal adhesions, whereas it is colocalized with the integrin at the ruffling edges of the cells. ICAP-1α induced a rapid disruption of focal adhesions, which may result from the ability of ICAP-1α to inhibit the association of β_1A integrin with talin, which is crucial for the assembly of these structures. ICAP-1α-mediated dispersion of β_1A integrins is not observed with β_1D integrins that do not bind ICAP. This strongly suggests that ICAP-1α action depends on a direct interaction between ICAP-1α and the cytoplasmic domain of the β₁ chains. Altogether, these results suggest that ICAP-1α plays a key role in cell adhesion by acting as a negative regulator of β₁integrin avidity.

Footnotes

↵* This work was supported in part by the Fédération Nationale des Ligues Contre le Cancer, the CNRS (Program Biologie Cellulaire: du Normal au Pathologique), and the Association pour la Recherche contre le Cancer.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.
↵¶ Recipient of a fellowship from the Ministère de la Recherche and the Association pour la Recherche contre le Cancer and presently supported by a Marie-Curie fellowship.
↵** To whom correspondence should be addressed. Tel.: 33-476-54-95-70; Fax: 33-476-54-94-25; E-mail: marc.block@ujf-grenoble.fr.
Published, JBC Papers in Press, December 7, 2002, DOI 10.1074/jbc.M211258200
Abbreviations:

CHO

Chinese hamster ovary

CaMKII

calmodulin-dependent protein kinase of type II

ICAP-1α

integrin cytoplasmic domain-associated protein-1α

PBS

phosphate-buffered saline

BSA

bovine serum albumin

VPM

ventral plasma membrane
- Received November 4, 2002.
The American Society for Biochemistry and Molecular Biology, Inc.