Cell adaptive response to extracellular matrix density is controlled by ICAP-1-dependent beta1-integrin affinity.
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.
Millon-Frémillon
Angélique
A
Institut National de la Santé et de la Recherche Médicale U823, France.
Bouvard
Daniel
D
Grichine
Alexei
A
Manet-Dupé
Sandra
S
Block
Marc R
MR
Albiges-Rizo
Corinne
C
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
C512603:ICAP-1 protein, mouse; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D016608:Talin