title: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U823, France.
authors.forename: Angélique
authors.initials: A
authors.lastname: Millon-Frémillon
authors.forename: Daniel
authors.initials: D
authors.lastname: Bouvard
authors.forename: Alexei
authors.initials: A
authors.lastname: Grichine
authors.forename: Sandra
authors.initials: S
authors.lastname: Manet-Dupé
authors.forename: Marc R
authors.initials: MR
authors.lastname: Block
authors.forename: Corinne
authors.initials: C
authors.lastname: Albiges-Rizo
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology*; D022001:Focal Adhesions; D019012:Integrin beta1 / Q000737:chemistry / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011487:Protein Conformation; D016608:Talin / Q000378:metabolism
chemical_list: C512603:ICAP-1 protein, mouse; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D016608:Talin