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Published online
doi:10.1083/jcb.200707142
The Journal of Cell Biology, Vol. 180, No. 2, 427-441
The Rockefeller University Press, 0021-9525 $30.00
© Millon-Frémillon et al.
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Article

Cell adaptive response to extracellular matrix density is controlled by ICAP-1–dependent β1-integrin affinity



Angélique Millon-Frémillon1,2,3, Daniel Bouvard1,2,3, Alexei Grichine2,4, Sandra Manet-Dupé1,2,3, Marc R. Block1,2,3, and Corinne Albiges-Rizo1,2,3

1 Institut National de la Santé et de la Recherche Médicale U823, 2 Université Joseph Fourier, 3 Centre National de la Recherche Scientifique, Equipe de Recherche Labellisée 3148, and 4 Cell Imaging Platform, Institut Albert Bonniot, 38042 Grenoble Cedex 9, France

Correspondence to Corinne Albiges-Rizo: corinne.albiges-rizo{at}ujf-grenoble.fr

Cell migration is an integrated process requiring the continuous coordinated assembly and disassembly of adhesion structures. How cells orchestrate adhesion turnover is only partially understood. We provide evidence for a novel mechanistic insight into focal adhesion (FA) dynamics by demonstrating that integrin cytoplasmic domain–associated protein 1 (ICAP-1) slows down FA assembly. Live cell imaging, which was performed in both Icap-1–deficient mouse embryonic fibroblasts and cells expressing active β1 integrin, shows that the integrin high affinity state favored by talin is antagonistically controlled by ICAP-1. This affinity switch results in modulation in the speed of FA assembly and, consequently, of cell spreading and migration. Unexpectedly, the ICAP-1–dependent decrease in integrin affinity allows cell sensing of matrix surface density, suggesting that integrin conformational changes are important in mechanotransduction. Our results clarify the function of ICAP-1 in cell adhesion and highlight the central role it plays in the cell's integrated response to the extracellular microenvironment.

Abbreviations used in this paper: FA, focal adhesion; FN, fibronectin; ICAP-1, integrin cytoplasmic domain–associated protein 1; MEF, mouse embryonic fibroblast; MFI, mean fluorescence intensity; VASP, vasodilator-stimulated phosphoprotein; VN, vitronectin; WT, wild type.


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