Liprin-α1 affects the distribution of low-affinity β1 integrins and stabilizes their permanence at the cell surface

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-α1 as an essential regulator of integrin dynamics required for efficient cell motility. Here we investigated the effects of liprin-α1 expression on β1 integrin receptors. We found that increased levels of liprin-α1 affected the localization of inactive, low-affinity integrins, while increasing the average size of β1 integrin-positive focal adhesions. Although a direct interaction between β1 integrins and liprin-α1 could not be revealed biochemically, a striking colocalization between redistributed inactive β1 integrins and liprin-α1 was observed. The tight association of overexpressed and endogenous liprin-α1 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 β1 integrin internalization. On the other hand, depletion of endogenous liprin-α by small interfering RNA increased the rate of integrin internalization. Overall, these results support the hypothesis that liprin-α1 exerts its action on focal adhesion turnover by influencing the localization and stability of integrin receptors at the cell surface.