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 function of this interaction has not been identified. Here, we report that APP and FE65 are involved in regulation of cell movement. APP and FE65 colocalize with actin and Mena, an Abl-associated signaling protein thought to regulate actin dynamics, in lamellipodia. APP and FE65 specifically concentrate with beta 1-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. Coexpression of APP and FE65 dramatically enhances the effect of APP on cell movement, 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-containing macromolecular complex, in regulation of actin-based motility.
Sabo
S L
SL
Laboratory of Molecular and Cellular Neuroscience and the Zachary and Elizabeth M. Fisher Center, The Rockefeller University, New York, New York 10021, USA. slsabo@ucdavis.edu
Ikin
A F
AF
Buxbaum
J D
JD
Greengard
P
P
D000199:Actins / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002451:Cell Compartmentation / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D003598:Cytoskeletal Proteins; D004285:Dogs; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D046911:Macromolecular Substances; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D011554:Pseudopodia / Q000378:metabolism
C091042:APBB1 protein, human; D000199:Actins; D016564:Amyloid beta-Protein Precursor; C486243:Apbb1 protein, mouse; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C102176:Enah protein, mouse; D019012:Integrin beta1; D046911:Macromolecular Substances; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins