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


ABSTRACT: 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.

SUBMITTER: Millon-Fremillon A 

PROVIDER: S-EPMC2213582 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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

Millon-Frémillon Angélique A   Bouvard Daniel D   Grichine Alexei A   Manet-Dupé Sandra S   Block Marc R MR   Albiges-Rizo Corinne C  

The Journal of cell biology 20080101 2


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 a  ...[more]

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