The Alzheimer amyloid precursor protein (APP) and FE65, an APP-binding protein, regulate cell movement

FE65 binds to the Alzheimer amyloid precursor protein (APP), but the functi on of this interaction has not been identified. Here, we report that APP an d FE65 are involved in regulation of cell movement. APP and FE65 colocalize with actin and Mena, an Abl-associated signaling protein thought to regula te actin dynamics, in lamellipodia. APP and FE65 specifically concentrate w ith beta1-integrin in dynamic adhesion sites known as focal complexes, but not in more static adhesion sites known as focal adhesions. Overexpression of APP accelerates cell migration in an MDCK cell wound-healing assay. Coex pression of APP and FE65 dramatically enhances the effect of APP on cell mo vement, probably by regulating the amount of APP at the cell surface. These data are consistent with a role for FE65 and APP, possibly in a Mena-conta ining macromolecular complex, in regulation of actin-based motility.