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The Alzheimer amyloid precursor protein (APP) and FE65, an APP-binding protein, regulate cell movement
S L Sabo1, A F Ikin, J D Buxbaum
1Laboratory 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
Abstract:
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.
Insights
Alzheimer amyloid precursor protein (APP) and FE65 regulate cell migration. They colocalize with actin and Mena in lamellipodia, enhancing cell movement and potentially impacting Alzheimer's disease research.
Area of Science:
- Cell Biology
- Neuroscience
- Biochemistry
Background:
- The interaction between FE65 and Alzheimer amyloid precursor protein (APP) is known, but its functional significance remains unclear.
- Cellular motility is crucial for various physiological processes, including development and disease pathogenesis.
Purpose of the Study:
- To investigate the role of APP and FE65 interaction in regulating cell movement.
- To elucidate the molecular mechanisms underlying APP and FE65-mediated cell migration.
Main Methods:
- Immunofluorescence microscopy to observe colocalization of APP, FE65, actin, Mena, and beta 1-integrin in lamellipodia and focal complexes.
- Cell migration assays, including wound-healing assays in MDCK cells, to assess the impact of APP and FE65 overexpression on cell movement.
Main Results:
- APP and FE65 were found to colocalize with actin and Mena in lamellipodia, and with beta 1-integrin in focal complexes.
- Overexpression of APP accelerated cell migration in a wound-healing assay.
- Coexpression of APP and FE65 significantly enhanced APP's effect on cell migration, suggesting FE65 regulates cell surface APP levels.
Conclusions:
- APP and FE65 play a significant role in regulating actin-based cell motility.
- The FE65-APP complex, potentially involving Mena, contributes to the regulation of cell movement, offering insights into cellular dynamics relevant to neurological conditions.