title: Liprin-alpha1 affects the distribution of low-affinity beta1 integrins and stabilizes their permanence at the cell surface.
abstract: 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.
authors.affiliation: Cell Adhesion Unit, Department of Neuroscience, San Raffaele University and San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Asperti
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pettinato
authors.forename: Ivan
authors.initials: I
authors.lastname: de Curtis
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002642:Chick Embryo; D004705:Endocytosis / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D022001:Focal Adhesions / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019012:Integrin beta1; C094398:PPFIA1 protein, human