The Alzheimer Amyloid Precursor Protein (APP) and Fe65, an APP-Binding Protein, Regulate Cell Movement
Open accessAbstract
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 β1-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.
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APP functions appear to be related to the FA pathway; integrin and APP share a number of interactors, including Fe65.
“These APP functions appear to be related to the FA pathway: integrin and APP share a number of interactors, including Fe65, a cytoplasmic adaptor protein that can simultaneously bind two NPXY motifs (carried by both integrins and APP) to form tripartite complexes [108].”
From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [108]
The Results section, “APP and FE65 in Integrin-based Focal Complexes” (page unavailable), reports that an APP–FE65 complex colocalizes with β1-integrins, supporting a link to focal complexes. The Discussion (page unavailable) says FE65 might interact with an integrin NPXY motif, but explicitly says it is not known whether the proteins interact simultaneously; it does not establish the claimed APP–FE65–integrin tripartite complex. (LLM, conf=0.88)
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Cites
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“APP and FE65 Regulate Cell Movement 1405 where r is the correlation and v is the covariance of two scalars, x and y .”
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- Authors
- Sabo, S. L., Ikin, A. F., Buxbaum, J. D., & Greengard, P.
- Affiliations
- Rockefeller University (US)
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2001-06-18
- Volume
- 153
- Issue
- 7
- Pages
- 1403-1414
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2150733
- OpenAlex
- W2150082378
- Cited by
- 237
- References
- 3
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 8 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 5 · 2015: 6 · 2014: 6 · 2013: 8 · 2012: 12
- FWCI
- 11.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG09464, P01AG009464)
- National Institute of General Medical Sciences (T32GM007524, GM07524)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- Fe65, cell migration, cell motility, actin dynamics, Middle East and North Africa, beta1 integrin, focal complexes, lamellipodia, cell adhesion, wound healing, MDCK cells
- MeSH terms
- Actins, Alzheimer Disease, Animals, Carrier Proteins, Cell Adhesion, Cell Compartmentation, Cell Line, Cell Movement, Cytoskeletal Proteins, Dogs, Humans, Microfilament Proteins, Nerve Tissue Proteins, Nuclear Proteins, Protein Binding, Pseudopodia, Amyloid beta-Protein Precursor, Integrin beta1, Protein Transport, Focal Adhesions, Macromolecular Substances
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