Integrins mediate the interaction between cells and extracellular matrix by assembling adhesive structures that need to be dynamically modulated to allow cell motility. We have recently identified liprin-alpha1 as an essential regulator of integrin dynamics required for efficient cell motility. Here we investigated the effects of liprin-alpha1 expression on beta1 integrin receptors. We found that increased levels of liprin-alpha1 affected the localization of inactive, low-affinity integrins, while increasing the average size of beta1 integrin-positive focal adhesions. Although a direct interaction between beta1 integrins and liprin-alpha1 could not be revealed biochemically, a striking colocalization between redistributed inactive beta1 integrins and liprin-alpha1 was observed. The tight association of overexpressed and endogenous liprin-alpha1 to the cytoplasmic side of the ventral plasma membrane suggested a possible role of liprin in stabilizing integrin receptors at the cell surface. In support of this hypothesis, we demonstrated an inhibitory effect of liprin overexpression on antibody-induced beta1 integrin internalization. On the other hand, depletion of endogenous liprin-alpha by small interfering RNA increased the rate of integrin internalization. Overall, these results support the hypothesis that liprin-alpha1 exerts its action on focal adhesion turnover by influencing the localization and stability of integrin receptors at the cell surface.
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