The Alzheimer Amyloid Precursor Protein (APP) and Fe65, an APP-Binding Protein, Regulate Cell Movement

doi:10.1083/jcb.153.7.1403

Published online 25 June 2001. doi:10.1083/jcb.153.7.1403

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© The Rockefeller University Press, 0021-9525/2001//1403 $5.00
The Journal of Cell Biology, Volume 153, Number 7, , 2001 1403-1414

Original Article

The Alzheimer Amyloid Precursor Protein (APP) and Fe65, an APP-Binding Protein, Regulate Cell Movement

Shasta L. Sabo^a, Annat F. Ikin^a^,b, Joseph D. Buxbaum^a^,b, and Paul Greengard^a

^a Laboratory of Molecular and Cellular Neuroscience and the Zachary and Elizabeth M. Fisher Center, The Rockefeller University, New York, New York 10021
^b Laboratory of Molecular Neuropsychiatry, Departments of Psychiatry and Neurobiology, Mount Sinai School of Medicine, New York, New York 10029
Center for Neuroscience, University of California at Davis, 1544 Newton Ct., Davis, CA 95616.(530) 757-8827(530) 754-6990

slsabo{at}ucdavis.edu

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 regulationof cell movement. APP and FE65 colocalize with actin and Mena,an Abl-associated signaling protein thought to regulate actindynamics, in lamellipodia. APP and FE65 specifically concentratewith β1-integrin in dynamic adhesion sites known as focalcomplexes, but not in more static adhesion sites known as focaladhesions. Overexpression of APP accelerates cell migrationin an MDCK cell wound–healing assay. Coexpression of APPand 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, possiblyin a Mena-containing macromolecular complex, in regulation ofactin-based motility.

Key Words: amyloid precursor protein • FE65 • Mena • cell movement • adhesion

Abbreviations used in this paper: APP, amyloid precursor protein;NGS, normal goat serum; PID, protein interaction domain.

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