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Publication : Cell adaptive response to extracellular matrix density is controlled by ICAP-1-dependent beta1-integrin affinity.

First Author  Millon-Frémillon A Year  2008
Journal  J Cell Biol Volume  180
Issue  2 Pages  427-41
PubMed ID  18227284 Mgi Jnum  J:196096
Mgi Id  MGI:5486544 Doi  10.1083/jcb.200707142
Citation  Millon-Fremillon A, et al. (2008) Cell adaptive response to extracellular matrix density is controlled by ICAP-1-dependent beta1-integrin affinity. J Cell Biol 180(2):427-41
abstractText  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 beta(1) 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.
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