Disruption of focal adhesions by integrin cytoplasmic domain-associated protein-1α

Abstract

Regulation of integrin affinity and clustering plays a key role in the control of cell adhesion and migration. The protein ICAP-1α (integrin cytoplasmic domain-associated protein-1α) binds to the cytoplasmic domain of the β1A integrin and controls cell spreading on fibronectin. Here, we demonstrate that, despite its ability to interact with β1A integrin, ICAP-1α is not recruited in focal adhesions, whereas it is colocalized with the integrin at the ruffling edges of the cells. ICAP-1α induced a rapid disruption of focal adhesions, which may result from the ability of ICAP-1α to inhibit the association of β1A integrin with talin, which is crucial for the assembly of these structures. ICAP-1α-mediated dispersion of β1A integrins is not observed with β1D integrins that do not bind ICAP. This strongly suggests that ICAP-1α action depends on a direct interaction between ICAP-1α and the cytoplasmic domain of the β1 chains. Altogether, these results suggest that ICAP-la plays a key role in cell adhesion by acting as a negative regulator of β1 integrin avidity.