beta2-adaptin binds actopaxin and regulates cell spreading, migration and matrix degradationbeta2-adaptin actopaxin结合,调节细胞扩散、迁移和矩阵退化.pdfVIP

Beta2-Adaptin Binds Actopaxin and Regulates Cell Spreading, Migration and Matrix Degradation 1 1 2 1 Jeanine Pignatelli , Matthew C. Jones , David P. LaLonde , Christopher E. Turner * 1 Department of Cell and Developmental Biology, State University of New York, Upstate Medical University, Syracuse, New York, United States of America, 2 Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York, United States of America Abstract Cell adhesion to the extracellular matrix is a key event in cell migration and invasion and endocytic trafficking of adhesion receptors and signaling proteins plays a major role in regulating these processes. Beta2-adaptin is a subunit of the AP-2 complex and is involved in clathrin-mediated endocytosis. Herein, b2-adaptin is shown to bind to the focal adhesion protein actopaxin and localize to focal adhesions during cells spreading in an actopaxin dependent manner. Furthermore, b2- adaptin is enriched in adhesions at the leading edge of migrating cells and depletion of b2-adaptin by RNAi increases cell spreading and inhibits directional cell migration via a loss of cellular polarity. Knockdown of b2-adaptin in both U2OS osteosarcoma cells and MCF10A normal breast epithelial cells promotes the formation of matrix degrading invadopodia, adhesion structures linked to invasive migration in cancer cells. These data therefore suggest that actopaxin-dependent recruitment of the AP-2 complex, via an interaction with b2-adaptin, to focal adhesions mediates cell polarity and migration and that b2-adaptin may control the balance between the formation of normal cell adhesions and invasive adhesion structures. Citation: Pignatelli J, Jones MC, LaLonde DP, Turner