Beta2-adaptin binds actopaxin and regulates cell spreading, migration and matrix degradation.
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, β2-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, β2-adaptin is enriched in adhesions at the leading edge of migrating cells and depletion of β2-adaptin by RNAi increases cell spreading and inhibits directional cell migration via a loss of cellular polarity. Knockdown of β2-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 β2-adaptin, to focal adhesions mediates cell polarity and migration and that β2-adaptin may control the balance between the formation of normal cell adhesions and invasive adhesion structures.
Department of Cell and Developmental Biology, State University of New York, Upstate Medical University, Syracuse, New York, USA.
Jeanine
J
Pignatelli
Matthew C
MC
Jones
David P
DP
LaLonde
Christopher E
CE
Turner
D033966:Adaptor Protein Complex beta Subunits / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D005109:Extracellular Matrix / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D011485:Protein Binding; D014945:Wound Healing; D000096985:Calponins
D033966:Adaptor Protein Complex beta Subunits; D008840:Microfilament Proteins; C581558:AP2B1 protein, human; C486590:PARVA protein, human; D000096985:Calponins