Abstract
Regulation of integrin affinity and clustering plays a key role in the control of cell adhesion and migration. The protein ICAP-1 alpha (integrin cytoplasmic domain-associated protein-1 alpha) binds to the cytoplasmic domain of the beta(1A) integrin and controls cell spreading on fibronectin. Here, we demonstrate that, despite its ability to interact with beta(1A) integrin, ICAP-1 alpha is not recruited in focal adhesions, whereas it is colocalized with the integrin at the ruffling edges of the cells. ICAP-1 alpha induced a rapid disruption of focal adhesions, which may result from the ability of ICAP-1 alpha to inhibit the association of beta(1A) integrin with talin, which is crucial for the assembly of these structures. ICAP-1 alpha-mediated dispersion of beta(1A) integrins is not observed with beta(1D) integrins that do not bind ICAP. This strongly suggests that ICAP-1 alpha action depends on a direct interaction between ICAP-1 alpha and the cytoplasmic domain of the beta(1) chains. Altogether, these results suggest that ICAP-1 alpha plays a key role in cell adhesion by acting as a negative regulator of beta(1) integrin avidity.
Highlights
Regulation of integrin affinity and clustering plays a key role in the control of cell adhesion and migration
ICAP-1␣ induced a rapid disruption of focal adhesions, which may result from the ability of ICAP-1␣ to inhibit the association of 1A integrin with talin, which is crucial for the assembly of these structures
Using purified ventral membrane preparation from HeLa cells, we never observed ICAP-1␣ colocalized with vinculin or talin, which were used as markers of focal adhesions
Summary
Regulation of integrin affinity and clustering plays a key role in the control of cell adhesion and migration. In this report we show that ICAP-1␣, despite its ability to interact directly and with the 1 integrin cytoplasmic domain in vitro, was never observed in focal adhesions. Analyzed the effect of ICAP-1␣ on the organization of these structures and showed that this protein was able to disorganize focal adhesions in a manner dependent on its direct interaction with the 1 cytoplasmic tail.
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